{"id":953,"date":"2026-08-14T19:28:16","date_gmt":"2026-08-14T19:28:16","guid":{"rendered":"https:\/\/psblab.org\/?p=953"},"modified":"2026-08-14T19:38:56","modified_gmt":"2026-08-14T19:38:56","slug":"mitochondrial-transplantation-really","status":"publish","type":"post","link":"https:\/\/psblab.org\/?p=953","title":{"rendered":"Mitochondrial Transplantation &#8211; REALLY?!"},"content":{"rendered":"<h3>(Warning &#8211; this post contains swearing. Once you&#8217;ve read it you&#8217;ll understand why)<\/h3>\n<p>Anyone who follows mitochondrial research closely will be aware of a phenomenon that&#8217;s appeared in the mito&#8217; literature in recent years &#8211; namely the concept that mitochondria can be isolated from a tissue or cells, then delivered to a tissue or intravenously to combat all manner of disease conditions.<\/p>\n<p>Yes REALLY!<\/p>\n<p><iframe loading=\"lazy\" title=\"YouTube video player\" src=\"https:\/\/www.youtube.com\/embed\/P4d-yBkrmsM?si=ApLZ128ZpRelwarS\" width=\"560\" height=\"315\" frameborder=\"0\" allowfullscreen=\"allowfullscreen\"><\/iframe><\/p>\n<p>Such autologous mitochondrial transplantation shares many parallels with the concept of stem cell transplantation, including (as will be discussed here) a propensity for crap methods and data.<\/p>\n<p>The first <a href=\"https:\/\/journals.physiology.org\/doi\/full\/10.1152\/ajpheart.00567.2008\">studies<\/a> suggesting this strategy came from the McCully lab at Harvard&#8217;s Boston Children&#8217;s Hospital, showing that injected mitochondria could lower infarct size in a rabbit model of myocardial ischemia (heart attack) by around a 50%.\u00a0 There has since been a <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=%22mitochondrial+transplantation%22\">plethora<\/a> of studies showing benefits of mitochondrial transplant for ischemia in other tissues (e.g., brain, liver) plus to treat many other conditions. <a href=\"https:\/\/link.springer.com\/article\/10.1186\/s12967-021-02878-3\">Here&#8217;s a review<\/a> covering various studies so far in the field of ischemia. The mechanistic claims behind this approach are quite bold &#8211; namely that mitochondria can be taken up into cells and can improve mito&#8217; function within them.<\/p>\n<p>Despite some promising findings, there has also been a steady <a href=\"https:\/\/www.jci.org\/articles\/view\/124944\/pdf\">backlash<\/a>, <a href=\"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.119.316291\">questioning<\/a> the fundamental mechanism by which any of this could work. Some of the specific issues raised are:<\/p>\n<p>(1) Mitochondria are known to regulate their Ca2+ levels within a tight window, and elevated Ca2+ (~100uM) is toxic to mitochondria, triggering the permeability transition pore, a key step in cell death. The free Ca2+ concentration outside cells (~2 mM) makes it highly unlikely any mitochondria could survive in such an environment, before entering cells.<\/p>\n<p>(2) The amounts of mitochondria that can achieve these effects are minuscule. The AJP paper mentioned above delivered ~6 million mitochondria to the infarct region of a rabbit heart. If one mito&#8217; is a 0.3 micron diameter sphere <a href=\"http:\/\/dx.doi.org\/10.3791\/51682\">(to use value determined by the same authors)<\/a> then it has a volume of ~1.4 E-20 m^3 (14 attoliters). A typical cardiomyocyte (10x10x100 microns) has a volume of 1 E-14 m^3 (10 femtoliters), and cardiomyocytes are ~30% mitochondria by volume. So, a heart cell would contain about 200,000 mitochondria, and therefore 6 million mito&#8217;s is about 30 cells&#8217; worth. Even if we pull a commonly cited value <a href=\"https:\/\/elifesciences.org\/articles\/23908\">from the literature<\/a> (based on zero evidence) that a heart cell contains 8000 mitochondria, then 6 million mito&#8217;s is still only 750 cells&#8217; worth. That&#8217;s not much.<\/p>\n<p>(3) Due to the evolutionary connection between mitochondria and bacteria, mitochondrial proteins are highly immunogenic, and indeed many auto-immune diseases such as lupus exhibit autoantibodies against mito&#8217; proteins. This has led to proposals that injected mito&#8217;s may simply trigger an immune response that accounts for their effects, as discussed extensively <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31734316\/\">here<\/a>. Rigorous experiments in immune compromised mice to rule out this mechanism have yet not been performed.<\/p>\n<p><span style=\"text-decoration: underline;\">In sum, it&#8217;s fair to say that a non-zero number of people in the mitochondrial research field are highly skeptical about this whole mito&#8217; transplant thing, especially when it comes to the details of how it actually works.<\/span><\/p>\n<p>&nbsp;<\/p>\n<p><strong>Onward Into Humans!<\/strong><\/p>\n<p>Despite these concerns, the first <a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0022522320331421?via%3Dihub\">human clinical studies<\/a> of mito&#8217; transplantation (MT) have already occurred in pediatric patients. The subjects of this 2021 paper were pediatric patients given ECMO (extracorporeal membrane oxygenation) to treat cardiac ischemic injury that occurred during a surgical procedure, with the ischemia itself treated by revascularization, and MT performed 1 day later. Some patients in this paper were part of an<a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0022522317302581\"> earlier published study<\/a>.<\/p>\n<p>The enrollment period for the study is given as 2002-2018, and the paper states that MT between May 2015 and July 2016 was under an IRB protocol, and then between July 2016 and December 2018 patients were enrolled in a <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT02851758?term=NCT02851758\">clinical trial<\/a>. The NCT record lists a trial start date of August 2017, so there&#8217;s a period of over a year (July 2016 &#8211; August 2017) in which patients were apparently given MT while enrolled in a clinical trial that hadn&#8217;t actually started yet.<\/p>\n<p>A somewhat bigger problem with these time frames is that the 10 MT patients must have been during the years 2015-2018, whereas the 14 controls were spread across a 16 year period (2002-2018). This &#8220;era effect&#8221; (which, to be fair, is acknowledged in the paper) raises the possibility that at least some of the effects of MT are attributable to changes in the clinical management of these patients since 2002.<\/p>\n<p>Nevertheless, additional human <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT04998357\">clinical trials<\/a> are <a href=\"https:\/\/link.springer.com\/epdf\/10.1007\/s40472-024-00428-6?sharing_token=VKpyDcau6zVGriAmPB8WLve4RwlQNchNByi7wbcMAY6wHkEdaxg4_HyMGJq416yHtsbNfOqapwLS0wReX_v7NfPJWmtdY7jXQh-gtIJ1pyzWXeurZNqbCEESxMhOqE-ZyzgmJW3ThZrfCFoUFBWXRCL6KvuyCw6xMlPhGMJqC1g%3D\">underway<\/a> in stroke patients, and on we march. Here&#8217;s a<a href=\"https:\/\/clinicaltrials.gov\/study\/NCT06020742\"> study taking mito&#8217;s from urine stem cells<\/a> and injecting them into oocytes for IVF (taking the piss?). This one <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT07066267\">does the same<\/a> but gets the mito&#8217;s from adipocytes instead. \u00a0<a href=\"https:\/\/clinicaltrials.gov\/study\/NCT04976140\">This one<\/a> takes mito&#8217;s from umbilical stem cells and uses them to treat polymyositis (a rare muscle disease). It ended in 2024 but hasn&#8217;t posted any results yet.\u00a0 Another <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT06017869\">study<\/a> uses mito&#8217;s from placenta to treat the mito&#8217; disease Pearson Syndrom. It&#8217;s run by a company called <a href=\"https:\/\/minoviatx.com\/\">Minovia therapeutics<\/a>, who apparently are <em>&#8220;Harnessing the therapeutic power of mitochondria.&#8221;<\/em>\u00a0 Here&#8217;s another trial of <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT05094011\">mito&#8217; transplant for Parkinson&#8217;s<\/a> disease, and another one for <a href=\"https:\/\/clinicaltrials.gov\/study\/NCT05669144\">patients<\/a> undergoing cardiac bypass graft surgery.<\/p>\n<p>Naturally, there are lots of biotech&#8217; companies in this area, because there&#8217;s money to be made in selling people on a cool new therapy idea. In addition to <a href=\"https:\/\/minoviatx.com\/\">Minovia<\/a> just mentioned, we have <a href=\"https:\/\/cellvie.bio\/\">Cellvie<\/a>, <a href=\"https:\/\/mitrix.bio\/\">Mitrix Bio<\/a>, <a href=\"http:\/\/www.paeanbio.com\/\">Paean Bio<\/a>, <a href=\"https:\/\/www.luca-science.com\/\">LUCA sciences<\/a>, <a href=\"https:\/\/www.mitosenseinc.com\/\">MitoSense<\/a>, and <a href=\"https:\/\/www.taimito.com\/new\">TaiMito<\/a>. It is somewhat troubling that many of these companies have well-known and highly respected members of the mitochondrial research community on their scientific advisory boards.<\/p>\n<p>Overall <span style=\"text-decoration: underline;\">it&#8217;s fair to say that the cat is well and truly out of the effing bag when it comes to shoving mito&#8217;s into humans<\/span>!\u00a0 Surely the underlying animal data to support such trials is solid, right?<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Extraordinary Claims Require Extraordinary Evidence, But Unfortunately The Evidence is a Bit Shit.<\/strong><\/p>\n<p><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0022522323004348?via%3Dihub\">Here&#8217;s a study<\/a> looking at mito&#8217; transplant in pigs from 2023 (i.e., after the human studies mentioned above). As seen below (and explained in more detail on <a href=\"https:\/\/pubpeer.com\/publications\/F9E37B7E47BEB49AC1979C850F411D\">PubPeer<\/a>) someone seems to have a passion for using photoshop when preparing H&amp;E stained microscopy images&#8230;<\/p>\n<p><a href=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/MitoTx2-scaled.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-958\" src=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/MitoTx2-300x173.jpg\" alt=\"\" width=\"400\" height=\"236\" \/><\/a><\/p>\n<p>Similar <a href=\"https:\/\/pubpeer.com\/publications\/648356353EB88D8767A2C1AB66BD64\">shenanigans<\/a> are seen in another 2020 pig <a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S1053249820316259?via%3Dihub\">paper<\/a> from the same group&#8230;<\/p>\n<p><a href=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/MitoTx3-scaled.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-959\" src=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/MitoTx3-300x295.jpg\" alt=\"\" width=\"400\" height=\"394\" srcset=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/MitoTx3-300x295.jpg 300w, https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/MitoTx3-1024x1007.jpg 1024w, https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/MitoTx3-768x755.jpg 768w, https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/MitoTx3-1536x1510.jpg 1536w, https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/MitoTx3-2048x2013.jpg 2048w, https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/MitoTx3-305x300.jpg 305w\" sizes=\"auto, (max-width: 400px) 100vw, 400px\" \/><\/a><\/p>\n<p>Aside from evidence of data manipulation, there are basic concerns about the quality of the other data. For example, here are a selection of images of cardiac infarcts from mito&#8217; transplant studies across several labs and animal models&#8230;<\/p>\n<p><a href=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/infarcts-scaled.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-large wp-image-961\" src=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/infarcts-1024x805.jpg\" alt=\"\" width=\"584\" height=\"459\" srcset=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/infarcts-1024x805.jpg 1024w, https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/infarcts-300x236.jpg 300w, https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/infarcts-768x604.jpg 768w, https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/infarcts-1536x1207.jpg 1536w, https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/infarcts-2048x1610.jpg 2048w, https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/infarcts-382x300.jpg 382w\" sizes=\"auto, (max-width: 584px) 100vw, 584px\" \/><\/a><\/p>\n<p>The images are poor quality and out of focus. Some of them use inches for measurement (what is this, the <a href=\"https:\/\/www.youtube.com\/watch?v=NWhrf3pOESI\">darkages<\/a>?), some are washed out, others have weird shadow lines suggesting they were not photographed together. In some the hearts are <em>squashed<\/em> or the ventricle lumen is filled with clotted blood. Some have white reflections indicating they were photographed in too strong a light (which gives a false positive signal when quantifying infarct area). The ones on the top left look like they were sliced with a hacksaw. These are pig, rabbit and rat hearts, so they&#8217;re all large enough to photograph at high resolution. There are often no details provided on how infarct size was calculated from these images.<\/p>\n<p>For comparison, here&#8217;s what a high quality pig infarct image looks like, from a <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32760857\/\">paper<\/a> by David Lefer&#8217;s lab. You can clearly see the contrast and resolution, and the cardiac anatomy (left and right ventricle).<\/p>\n<p><a href=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/gr3-scaled.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-979\" src=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/gr3-1024x421.jpg\" alt=\"\" width=\"281\" height=\"122\" \/><\/a><\/p>\n<p>Here are some infarct images from much smaller mouse hearts in my lab (from <a href=\"https:\/\/elifesciences.org\/articles\/58573\">here<\/a>). You can see the contrast between white infarct and red live tissue. You can see the lumen of the LV, and the RV toward the lower right. Each image is accompanied by a pseudo-color map showing how pixel counts were used to distinguish infarct vs. live tissue.<\/p>\n<p><a href=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/Fig4-Supp2.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-962\" src=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/Fig4-Supp2.jpg\" alt=\"\" width=\"282\" height=\"219\" \/><\/a><\/p>\n<p>So, it&#8217;s reasonable to say that the primary animal data supporting the notion of putting mitochondria into human hearts is of questionable quality.\u00a0 There are <span style=\"text-decoration: underline;\">a lot more examples of problematic data<\/span> further down the page, but first&#8230;<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Let&#8217;s Make Some Mito&#8217;s!<\/strong><\/p>\n<p>Consider the methodology used to isolate mitochondria for transplant. Most studies in this area use a <a href=\"https:\/\/www.jove.com\/t\/51682\/rapid-isolation-purification-mitochondria-for-transplantation-tissue\">method published in 2014. \u00a0<\/a>A key step in the protocol is the use of a protease to digest muscle tissue. This technique was <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/925018\/\">pioneered by Charles Hoppel in the 1970s<\/a> and is routinely used in mitochondrial research because it releases mitochondria trapped between the myofibrils in muscle cells. The protease of choice is Subtilisin A, obtained from <em>Bacillus licheniformis<\/em> (in reality <a href=\"https:\/\/www.sigmaaldrich.com\/US\/en\/product\/sigma\/p5380\">from Sigma<\/a>). Fun-fact&#8230; a version of the same enzyme is a component of modern laundry detergents.<\/p>\n<p>One of the known problems with using proteases to isolate mitochondria is it&#8217;s almost impossible to get rid of the protease in subsequent wash steps. A common solution (used here) is to dump in a large quantity of another protein such as bovine-serum-albumin (BSA) to give the protease <em>something else to chew on<\/em> so it doesn&#8217;t keep on digesting and destroy the mitochondria.\u00a0 One would hope that any proteins used during the mito&#8217; prep would at least be manufactured to clinical (<a href=\"https:\/\/www.fda.gov\/drugs\/pharmaceutical-quality-resources\/facts-about-current-good-manufacturing-practice-cgmp\">GMP<\/a>) specifications. Alas, the <a href=\"https:\/\/www.sigmaaldrich.com\/US\/en\/product\/sial\/a7906\">BSA used here<\/a> is simply heat-fractionated cheap stuff from Sigma, which is loaded with lipids and various heme-related pigments. Even though <em>Bacillus licheniformis<\/em> is gram-positive and doesn&#8217;t generate endotoxin, I wonder if the patients undergoing this procedure are told that the <em>&#8220;autologous mitochondria&#8221;<\/em> being infused are very likely contaminated with remnants of a bacterial enzyme plus a crude fraction from cow blood?<\/p>\n<p>After digesting the tissue, many mitochondrial preparations use differential centrifugation to separate mitochondria from other cell components. First a low speed spin (~1000 x <em>g<\/em>) gets rid of cell debris and nuclei, then a series of high-speed spins (~10,000 x <em>g<\/em>) pellet the mitochondria and wash away cell components of a similar size that would contaminate the prep&#8217; (fragments of ER, SR, peroxisomes, microsomes, etc).<\/p>\n<p>Instead, <a href=\"https:\/\/www.jove.com\/t\/51682\/rapid-isolation-purification-mitochondria-for-transplantation-tissue\">this method<\/a> simply passes the cell homogenate through 3 filters (2 x 40 micron, then 10 micron) then a centrifugation step to pellet the mito&#8217;s. This is problematic because filtration will get rid of things bigger than the filter size, but anything smaller will pass through &#8211; including all those mito-sized membrane fragments I just mentioned, plus the bacterial protease and BSA. And don&#8217;t forget the blood!\u00a0 Yes lots of blood, as evidenced by the red color of the <em>mito pellets<\/em> in the accompanying <a href=\"https:\/\/www.jove.com\/v\/51682\/rapid-isolation-purification-mitochondria-for-transplantation-tissue\">video<\/a>. Here&#8217;s a screen shot &#8211; that red stuff at the bottom of the tube is blood. Mitochondria are light brownish-green, not red.<\/p>\n<p><a href=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/mitoblood.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-989\" src=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/mitoblood.jpg\" alt=\"\" width=\"263\" height=\"270\" srcset=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/mitoblood.jpg 415w, https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/mitoblood-292x300.jpg 292w\" sizes=\"auto, (max-width: 263px) 100vw, 263px\" \/><\/a><\/p>\n<p>There&#8217;s also a mis-match in the paper&#8217;s claims about particle size and purity of the mito&#8217; preparation. It is claimed 0.18g of tissue yields 2 x 10^10 mitochondria, and the mito&#8217;s are 0.3 microns across. That&#8217;s a total mito&#8217; volume of just 0.3 microliters, which should not be a visible pellet, and yet the <a href=\"https:\/\/www.jove.com\/v\/51682\/rapid-isolation-purification-mitochondria-for-transplantation-tissue\">video<\/a> clearly shows a pellet (maybe 50 microliters) yielding a milky suspension. The paper makes bold claims about the <em>purity<\/em> of the preparation, but includes no measurements to show the removal of other contaminating cell fractions (e.g., western blot for other membranes). There are some electron micrographs, but no description of how such images were analyzed to arrive at the claimed &#8220;&lt;0.001% contamination by non-mitochondrial particles.&#8221;\u00a0 A\u00a0<a href=\"https:\/\/en.wikipedia.org\/wiki\/Occam%27s_razor\">simpler interpretation<\/a> is that the mito&#8217; prep cannot possibly be 99.999% mitochondria, and it is very likely contaminated with other membrane fractions and blood (for the record, red blood cells can easily pass through a 10 micron filter).<\/p>\n<p>The method paper also claims mitochondria were counted using a hemocytometer. Here&#8217;s a picture from my lab of some cardiomyocytes on a hemocytometer grid.\u00a0 Each small square (bounded by single lines) is 50 microns across. Those small specks of dirt are maybe 2-3 microns across. I might be <a href=\"https:\/\/en.wikipedia.org\/wiki\/Myopia\">almost blind<\/a>, but I don&#8217;t think anyone with 20:20 vision could reasonably see and accurately count a bunch of 0.3 micron particles at such scale.<\/p>\n<p><a href=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/myocytes.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-965 alignnone\" src=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/myocytes.jpg\" alt=\"\" width=\"360\" height=\"309\" \/><\/a><\/p>\n<p>An <a href=\"https:\/\/www.jove.com\/files\/ftp_upload\/51682\/51682fig3highres.jpg\">image<\/a> from the paper shows some mito&#8217; particles accompanied by a single black 25 micron scale bar. I&#8217;ve added a ruler below the scale bar, then used it to draw in some actual 0.3 micron particles &#8211; the blue dots. Do the red things (mito&#8217;s) look like they have an average size the same as the blue things?<\/p>\n<p><a href=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/microns-scaled.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-967\" src=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/microns-1024x707.jpg\" alt=\"\" width=\"371\" height=\"259\" \/><\/a><\/p>\n<p>Lastly regarding methods, I&#8217;ll note that before this JoVE paper, the <a href=\"https:\/\/journals.physiology.org\/doi\/full\/10.1152\/ajpheart.00883.2012\">2013 AJP<\/a> mito transplant paper isolated mitochondria from skeletal muscle in the chest wall. It refers to an earlier <a href=\"https:\/\/journals.physiology.org\/doi\/full\/10.1152\/ajpheart.00567.2008\">2009 AJP<\/a> mito transplant paper for the method. That paper isolated mitochondria from heart tissue, and lists 2 references for the method. The <a href=\"https:\/\/www.ovid.com\/jnls\/ccmjournal\/fulltext\/10.1097\/01.ccm.0000278604.93569.27~cytochrome-c-oxidase-dysfunction-in-sepsis\">first<\/a> of those papers has no methods section and no information on how to isolate mitochondria (although it does refer to a <a href=\"https:\/\/www.ovid.com\/jnls\/shockjournal\/fulltext\/10.1097\/01.shk.0000108400.56565.ab~competitive-and-noncompetitive-inhibition-of-myocardial\">paper <\/a>that used differential centrifugation). The <a href=\"https:\/\/watermark02.silverchair.com\/61-3-365.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAoYwggKCBgkqhkiG9w0BBwagggJzMIICbwIBADCCAmgGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMnLBr1-IpEiYowFIVAgEQgIICOYseilykVAlV61VoFRbHhbKCr1X8O9dXTKIavNNZT4ZMIIcv5r1Fnf0LL7lMImrx3kNP2ogTD1FTLT6_fMetWFzr3eytA4-hNnBnGO7T2EOM5ezTpaGlO59bMIrpth9v49LMJoHJEWn4O85hlUOFVlelmMAzlFtDPV2-5V0GI2RJ45_-6E6bKtFVECvwrdnjW2C60mziPtTB9e1x-SLu2q6VtY3_nXSqGRfHeyqnEolWsKushRY7HW39li-biEevjcA4tWUJVq9WKjudPn86SUaoHvOGjC2h7N5KBlFOe6lP_P98ehJRtSxUJw-9tqisB9zzHxa-aUcu2MkMUeMw1EEO_YSeg8djKYKV6idVZPu4oXTSDsdhGbBI63oN2-_ceMWyT2NkhfCkKqZtLm1_flqj0xoAKwnXLmm07SkPP2Gk50si32jnk8iqVVkz13aYfRrET9ygW4jWkJyol0Y_uA_JOeTe54ZPEk0h3lB9AnMThvm480x6GNbE_dNO4plzK3sPvzM2pnt--m1qfXA8uEtQOchfE-CC9I0vaclX8D4PffYpYgzDL-AAbdFpLPTmT5T3Stzd-7OttbmK3KBTAD-IJSEWleQddcQMbbCpJ0dzaUpm0KF_3p-G67ZSdxF_sih0mok2AAqnFQlSDUUGWOlnA4oVMg4dUIv5oGmlMdIIOFdvYw-W2Y4qqPrV6hd_YWVeQWq4wRdiwumIIo5WJ94sYim6sv7Gyfcf07FEBnh0N4MLXqrKXHi_\">second<\/a> is a review article about cardioprotection, with no methods.\u00a0 Likewise, the<a href=\"https:\/\/journals.physiology.org\/doi\/full\/10.1152\/ajpheart.00567.2008\"> 2009 AJP<\/a> paper cites a method to measure mito&#8217; respiration, but the <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/12388274\/\">cited paper<\/a> is on a different topic and says nothing about mito&#8217; respiration.<\/p>\n<p>So, it seems the animal studies used to support going to clinical trials relied on a crude mito&#8217; isolation method from various tissues, and then a new and very different filtration method was invented and is being pushed for human studies, despite very little evidence that it actually makes anything resembling mitochondria.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>But What About ATP ?!?!<\/strong><\/p>\n<p>Key questions for anyone preparing mitochondria include&#8230; Do they consume oxygen?\u00a0 Do they have a membrane potential?\u00a0 Are their membranes intact?\u00a0 Can they <span style=\"text-decoration: underline;\">make<\/span> ATP?\u00a0 This last question appears to have been mis-applied by the proponents of mito&#8217; transplantation.<\/p>\n<p>All basic <a href=\"https:\/\/wwnorton.com\/books\/9780393884821\">biochemistry<\/a> or <a href=\"https:\/\/www.amazon.com\/Metabolism-at-Glance-J-Salway\/dp\/0470674717\">metabolism<\/a> books have a chapter on mitochondrial oxidative phosphorylation (Ox-Phos). Here&#8217;s the short version&#8230; (i) The Krebs&#8217; cycle burns metabolic acids to generate NADH. (ii) The electron transport chain passes electrons from NADH through respiratory complexes I-IV and onto oxygen. In doing so, the complexes pump protons out of mitochondria, generating a proton gradient or membrane potential. (iii) Oxygen is the terminal electron acceptor, and gets consumed and turned into water during this process. (iv) The energy in the proton gradient is used by complex V to make ATP from ADP and phosphate.\u00a0 Importantly, this whole process relies on mito&#8217; membranes being intact. Here&#8217;s an animated GIF I made when I was a grad student more than 30 years ago&#8230;<\/p>\n<p><a href=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/etcanim.gif\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-992\" src=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/etcanim.gif\" alt=\"\" width=\"162\" height=\"95\" \/><\/a><\/p>\n<p><span style=\"text-decoration: underline;\">For mitochondria to be functional, what matters is the RATE at which they generate ATP.\u00a0 Dead or non-functioning mitochondria still contain ATP, but it&#8217;s the ability to MAKE ATP that matters<\/span>.\u00a0 The <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/10100854\/\">proper way to do this<\/a> (as I did a mere 27 years ago) is to incubate mitochondria with a substrate (to feed the Krebs&#8217; cycle) plus some ADP, then take aliquots at regular time intervals, crash out the protein (to stop any ATP from being consumed) then measure the ATP. Finally, plot a graph of ATP vs. time and calculate the slope (rate). Ideally you do this +\/- an inhibitor of complex V (oligomycin) to make sure the ATP is actually coming from Ox-Phos.<\/p>\n<p>Is that what people isolating mito&#8217;s for transplant are doing? Nope. <a href=\"https:\/\/www.jove.com\/t\/51682\/rapid-isolation-purification-mitochondria-for-transplantation-tissue\">Instead\u00a0<\/a>you just slap the mito&#8217;s in a plate reader with some <a href=\"https:\/\/www.fishersci.com\/shop\/products\/atplite-m-1-000-assay-kit\/509049889\">ATP kit<\/a> reagents and a lysis buffer to break everything open, leave it for 10 minutes and do a single end-point measurement.\u00a0 <span style=\"text-decoration: underline;\"><strong>Let me be abundantly clear &#8211; what this method measures is how much ATP the mitochondria contain. This has FUCK ALL to do with how functional they are, and the rate at which they make ATP!<\/strong><\/span><\/p>\n<p>The assay does not (and indeed can not) measure mito&#8217; function, because everything is blown to shit by the lysis buffer.\u00a0 The fact this is now the standard method for making mito&#8217;s for transplantation (<a href=\"https:\/\/www-webofscience-com.ezpminer.urmc.rochester.edu\/wos\/woscc\/full-record\/WOS:000349301100022\">136 citations<\/a> so far) is shameful. The fact it got past peer review indicates the quality of that process at <a href=\"https:\/\/www.jove.com\/\">JoVE<\/a>. Surely human patients deserve better than this?<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Why Isolate Mitochondria When You Can Grow Them?<\/strong><\/p>\n<p>In 2022, a <a href=\"https:\/\/link.springer.com\/article\/10.1007\/s12035-022-02937-w\">paper<\/a> claimed that infusion of mitochondria can improve function in the hippocampus of aged mice. Unfortunately, as documented on <a href=\"https:\/\/pubpeer.com\/publications\/924331EB2AFA8615F307EE640D0F55\">PubPeer<\/a>, the western blots were a giant mess, which greatly undermines confidence that the authors know what they&#8217;re doing.<\/p>\n<p>This is unfortunate, because the lead author on the paper <a href=\"https:\/\/mitrix.bio\/team\/benedict-albensi-ph-d\/\">Benedict Albensi<\/a>, is a key scientific advisor for the company <a href=\"https:\/\/mitrix.bio\/\">Mitrix Bio<\/a>. Mitrix takes the cake when it comes to mitochondrial science fiction &#8211; they claim to be<em> growing mitochondria in a bioreacto<\/em>r, and they call them &#8220;mitlets&#8221;. <strong><em>For anyone remotely versed in mitochondrial biology, the notion that you can &#8220;grow mitochondria&#8221; outside of cells is complete bullshit.\u00a0 <\/em><\/strong>The <a href=\"https:\/\/www.mitonauts.com\/uploads\/1\/0\/6\/3\/10638122\/221009_mitrix_deck_full_ver_d.pdf\">reality<\/a> is a bit more simple&#8230; they take stem cells, grow those in a reactor, then isolate the mito&#8217;s and package them up in membranes for delivery.<\/p>\n<p>This all came to prominence recently because a group of folks calling themselves &#8220;<a href=\"https:\/\/www.mitonauts.com\/\">Mitonauts<\/a>&#8221; published a <a href=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/Mitonauts-challenge.pdf\">press release<\/a> claiming that the wait is over and we should all just embrace lab-grown mitochondria to combat aging!<\/p>\n<p>Those of you who know me will perhaps recall an article I wrote several years ago about the<a href=\"https:\/\/psblab.org\/?p=697\"> giant shit-show that is longevity biotechnology<\/a>, and this appears to be nothing different. A bunch of rich libertarians arguing for right-to-try and lax regulations, so they can apply a therapy with not very good supporting data (see above), to overcome a poorly understood pathologic state. They&#8217;re testing it on themselves, which I guess is slightly better than trying it on children.\u00a0 Stem cells didn&#8217;t work, but surely mitochondria isolated from stem cells will work. Hey it&#8217;s your money, who am I to tell you how to waste it?<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Why Inject Mito&#8217;s When You Can Just Eat Them?<\/strong><\/p>\n<p>Why go to all the bother of injecting or infusing mitochondria, when you can <a href=\"https:\/\/link.springer.com\/article\/10.1186\/s40035-026-00565-1\">just EAT them instead<\/a>?\u00a0 This is especially true if they&#8217;re plant mitochondria, because we all know that plant based diets are more healthy.\u00a0 Of course, the paper was absolutely loaded with manipulated images, as <a href=\"https:\/\/pubpeer.com\/publications\/87B5BE0D5ABEE63D4145D56A5DFCDB?\">documented on PubPeer<\/a>.\u00a0 <a href=\"https:\/\/forbetterscience.com\/2026\/07\/31\/schneider-shorts-31-07-2026-stackable-micro-credentials\/#tmit\">Leo Schneider has a nice write-up<\/a> of similar shenanigans from the same lab going back several years.<\/p>\n<p>My favorite is this example below, in which the HPLC data appear to be faked by pasting in the peaks onto the baseline. The problem is whoever did this forgot to change the colors, so they ended up with a black baseline which magically switches to a blue line for the peaks, then back to black again.\u00a0 Both the authors and the editors of the journal were notified, and neither have responded to indicate they&#8217;re even remotely interested in dealing with this.<\/p>\n<p><a href=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/Slide-5-scaled.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-large wp-image-972\" src=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/Slide-5-1024x629.jpg\" alt=\"\" width=\"584\" height=\"359\" srcset=\"https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/Slide-5-1024x629.jpg 1024w, https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/Slide-5-300x184.jpg 300w, https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/Slide-5-768x472.jpg 768w, https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/Slide-5-1536x944.jpg 1536w, https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/Slide-5-2048x1259.jpg 2048w, https:\/\/psblab.org\/wp-content\/uploads\/2026\/08\/Slide-5-488x300.jpg 488w\" sizes=\"auto, (max-width: 584px) 100vw, 584px\" \/><\/a><\/p>\n<p>&nbsp;<\/p>\n<p><strong>This Shit is Everywhere!<\/strong><\/p>\n<p>Lest anyone think the problems in this field are limited to a few labs and obscure journals, here are just a few more of the papers on mitochondrial transplantation in which I and others have found &#8220;problems&#8221;&#8230;<\/p>\n<ul>\n<li>Here&#8217;s <a href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.13153\">one I found this week<\/a>, on mito transplant for muscle wasting. Image overlap reported on <a href=\"https:\/\/pubpeer.com\/publications\/DD4FC1E66240C06FFA65423171D5CF\">PubPeer, <\/a>authors notified, and apparently this will be corrected.<\/li>\n<\/ul>\n<ul>\n<li>This <a href=\"https:\/\/doi.org\/10.3389\/fphar.2017.00241\">paper<\/a> is about mito&#8217; transplant to treat fatty liver disease, but (as explained on <a href=\"https:\/\/pubpeer.com\/publications\/393DF9A2CCD4ADBA9F39340DCD07A7\">PubPeer<\/a>) the authors reused some images in <a href=\"https:\/\/doi.org\/10.3390\/ijms20184643\">another paper<\/a>, which doesn&#8217;t instill confidence in their lab&#8217;s data management.<\/li>\n<\/ul>\n<ul>\n<li>Here&#8217;s <a href=\"https:\/\/www.ijbs.com\/v17p2021.htm\">another one<\/a> all about mito&#8217; transplant in melanoma, with <a href=\"https:\/\/pubpeer.com\/publications\/4783BBA51ACD08F7900D6F4C30FC2E\">dodgy western blots<\/a>. Supposedly the authors sent a correction to the journal in February 2024, but it hasn&#8217;t been corrected yet.<\/li>\n<\/ul>\n<ul>\n<li>The <a href=\"https:\/\/doi.org\/10.1038\/s41593-019-0486-0\">concept that mito&#8217;s are released from cells<\/a> also has <a href=\"https:\/\/pubpeer.com\/publications\/5549D5D042341EDBC8E8B302BCED2C\">problematic data<\/a>.\u00a0 Mito transplant into stem cells is also <a href=\"https:\/\/pubpeer.com\/publications\/68E8555189207B60B6833B3D7C41F3\">problematic<\/a>.<\/li>\n<\/ul>\n<ul>\n<li>Here&#8217;s a <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36922820\/\">paper<\/a> where they did mito&#8217; transplant and claimed to do CPR on rats, at a rate of 300 beats per minute. That&#8217;s 5 times a second! The best gamers in the world can maybe do 6 mouse clicks a second, so the notion that anyone could do CPR with any control over depth or accuracy of compressions at a rate of 5Hz, is not credible. No response on <a href=\"https:\/\/pubpeer.com\/publications\/A3E9ED6DAA6D90F8FA481509876B1F\">PubPeer<\/a> yet.<\/li>\n<\/ul>\n<ul>\n<li>This <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34085316\/\">paper<\/a> claims tunnelling nanotubes can transport mitochondria between cells in the hipoocampus. The western blots are\u00a0<a href=\"https:\/\/pubpeer.com\/publications\/64EA1D0C27B8A500F9D6D4BECFD69E#0\">laughable<\/a>.<\/li>\n<\/ul>\n<ul>\n<li>This <a href=\"https:\/\/www.nature.com\/articles\/s41586-024-08439-0\">paper<\/a> on mito&#8217; transfer in the tumor microenvironment got <a href=\"https:\/\/pubpeer.com\/publications\/0A7A0534D4CD5410C1BDF90C1F38A8#0\">called out<\/a> for some <em>numerical irregularities<\/em> (aka. creative use of copy\/paste in Excel), and then swiftly corrected. Nothing to see here, move along please.<\/li>\n<\/ul>\n<ul>\n<li><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39940960\/\">This one<\/a> is about mito&#8217; transfer in cancer stem cells.\u00a0 You guess it, <a href=\"https:\/\/pubpeer.com\/publications\/E8B2177F43C081922123C718436652#0\">crap western blots<\/a> again!\u00a0 <a href=\"https:\/\/pubpeer.com\/publications\/AB662CFB1BCBF2C3FB3ADB9A14A7DA\">Another paper<\/a> in the same area had some problems addressed in an erratum, then other problems raised later on PubPeer which have still not been resolved. Yet another <a href=\"https:\/\/pubpeer.com\/publications\/39E2843FAD1D8011ADC037938B8A4D\">paper<\/a> in the same area is very problematic.<\/li>\n<\/ul>\n<ul>\n<li><a href=\"https:\/\/www.ahajournals.org\/doi\/10.1161\/SVIN.122.000644\">Here&#8217;s one<\/a> I found just yesterday on mito&#8217; transplant\u00a0 in stroke, where the authors apparently had electron microscopy data on 94 specimens from 3 batches of mitochondria, but somehow chose to show 3 parts of the same image cropped differently as <a href=\"https:\/\/pubpeer.com\/publications\/65D1A9C7C3081550C90BD8F1CF593A\">evidence<\/a>.<\/li>\n<\/ul>\n<ul>\n<li>And here&#8217;s <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31281500\/\">a new one<\/a> from today, on mito&#8217; transfer for radiation toxicity in glioma. The <a href=\"https:\/\/pubpeer.com\/publications\/286D25C28DBC59E35F29914EFCD63E\">western blots are a joke<\/a>.<\/li>\n<\/ul>\n<p>Naturally, the field is awash with review articles, editorials and puff-pieces, talking up the whole idea of mito&#8217; transplant and how wonderful everything is.\u00a0 How do you think I found most of the problematic articles I flagged on PubPeer, for this blog post?\u00a0 That&#8217;s right &#8211; they&#8217;re the very same one being cited to support this madness.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Summary<\/strong><\/p>\n<p>It&#8217;s not looking good.\u00a0 The entire field of mitochondrial transfer and transplantation is flooded with crap data and methods. The <span style=\"text-decoration: underline;\"><strong>data from animal models being used to support human clinical trials is simply not fit for the task<\/strong><\/span>, and the clinical trials themselves are not much better. Money is pouring into the biotech&#8217; industry being built off this house-of-cards. Now the whole thing is being\u00a0hijacked by a bunch of libertarians and <em>right-to-try<\/em> millionaires (&#8220;<a href=\"https:\/\/www.mitonauts.com\/\">mitoNUTS<\/a>&#8220;) pushing for unregulated mito&#8217; therapy for aging and who knows what else.<\/p>\n<p>The field of mitochondrial research has a noble history. Shame on any bona-fide mitochondrial biologist who goes along with this crap without speaking out!<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>(Warning &#8211; this post contains swearing. Once you&#8217;ve read it you&#8217;ll understand why) Anyone who follows mitochondrial research closely will be aware of a phenomenon that&#8217;s appeared in the mito&#8217; literature in recent years &#8211; namely the concept that mitochondria &hellip; <a href=\"https:\/\/psblab.org\/?p=953\">Continue reading <span class=\"meta-nav\">&rarr;<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-953","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"_links":{"self":[{"href":"https:\/\/psblab.org\/index.php?rest_route=\/wp\/v2\/posts\/953","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/psblab.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/psblab.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/psblab.org\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/psblab.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=953"}],"version-history":[{"count":10,"href":"https:\/\/psblab.org\/index.php?rest_route=\/wp\/v2\/posts\/953\/revisions"}],"predecessor-version":[{"id":999,"href":"https:\/\/psblab.org\/index.php?rest_route=\/wp\/v2\/posts\/953\/revisions\/999"}],"wp:attachment":[{"href":"https:\/\/psblab.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=953"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/psblab.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=953"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/psblab.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=953"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}