{"id":3102,"date":"2026-07-23T18:46:11","date_gmt":"2026-07-23T22:46:11","guid":{"rendered":"https:\/\/haidut.me\/?p=3102"},"modified":"2026-07-23T18:46:11","modified_gmt":"2026-07-23T22:46:11","slug":"interfering-with-mitochondrial-dynamics-causes-cancer-by-driving-inflammation-no-carcinogen-mutation-required","status":"publish","type":"post","link":"https:\/\/haidut.me\/?p=3102","title":{"rendered":"Interfering with mitochondrial dynamics causes cancer (by driving inflammation); no carcinogen\/mutation required!"},"content":{"rendered":"<p>One of the rare studies that quietly lets the truth out in the open. Namely, that cancer is a metabolic\/inflammatory disease that does not need any oncogenic mutations to occur first. All that is needed is a process that interferes with mitochondrial dynamics (fission\/fusion), which then drives chronic inflammation in the cell, and finally cancer forms spontaneously! Unsurpisingly, the process that interfered with the mitochondrial dynamic was linked to elevated fatty acid oxidation (FAO). Conversely, blocking the inflammatory pathway resulting from suboptimal mitochondrial dynamics virtually arrests further cancer development. I wonder how long before that study gets retracted for &#8220;unspecified&#8221; reasons&#8230;<\/p>\n<p><a href=\"https:\/\/egastroenterology.bmj.com\/content\/4\/2\/e100408\">https:\/\/egastroenterology.bmj.com\/content\/4\/2\/e100408<\/a><\/p>\n<blockquote class=\"wp-embedded-content\" data-secret=\"hslWTer5R1\"><p><a href=\"https:\/\/scienceblog.com\/why-some-heavy-drinkers-grow-giant-mitochondria-that-guard-the-liver-for-a-while\/\">Why Some Heavy Drinkers Grow Giant Mitochondria That Guard the Liver, for a While<\/a><\/p><\/blockquote>\n<p><iframe loading=\"lazy\" class=\"wp-embedded-content\" sandbox=\"allow-scripts\" security=\"restricted\" style=\"position: absolute; visibility: hidden;\" title=\"&#8220;Why Some Heavy Drinkers Grow Giant Mitochondria That Guard the Liver, for a While&#8221; &#8212; ScienceBlog.com\" src=\"https:\/\/scienceblog.com\/why-some-heavy-drinkers-grow-giant-mitochondria-that-guard-the-liver-for-a-while\/embed\/#?secret=6eS3NBObhZ#?secret=hslWTer5R1\" data-secret=\"hslWTer5R1\" width=\"500\" height=\"282\" frameborder=\"0\" marginwidth=\"0\" marginheight=\"0\" scrolling=\"no\"><\/iframe><\/p>\n<p>&#8220;&#8230;And the surprise was what those giants could do. Using bench techniques that measure how hard a cell is breathing, plus a sweep of the liver\u2019s metabolites, the researchers saw alcohol-fed mice ramp up oxygen consumption, push out more NAD+ (the molecule alcohol notoriously drains), and <span style=\"text-decoration: underline;\"><strong>burn fat more efficiently<\/strong><\/span>. Not the picture of a poisoned cell at all. &#8221;<\/p>\n<p>&#8220;&#8230;The trouble is that the defence has a shelf life. New megamitochondria help; old ones turn on their host. As the giants persist, they take on damage, mutated mtDNA, broken proteins, and they can\u2019t be cleared away. Mitophagy, the cell\u2019s housekeeping system for junking spent mitochondria, needs them chopped small first, and these are far too big to swallow. So the damaged hulks pile up. Worse, they start <span style=\"text-decoration: underline;\"><strong>leaking their own DNA into the cell\u2019s interior, where it trips an ancient alarm system called cGAS-STING that\u2019s meant to detect invading viruses<\/strong><\/span>. <span style=\"text-decoration: underline;\"><strong>The liver, in effect, mistakes its own broken machinery for an infection and lights a slow inflammatory fire, the kind that scars tissue into fibrosis over years<\/strong><\/span>. To see what losing fission really does, the team engineered mice whose liver cells lack DRP1 entirely. These animals <span style=\"text-decoration: underline;\"><strong>developed elevated liver enzymes, fibrosis, and, by 12 to 18 months, spontaneous liver tumours. <span style=\"color: #ff0000; text-decoration: underline;\">No carcinogen required; jamming the [mitochondrial] dynamics was enough on its own<\/span><\/strong><\/span>.&#8221;<\/p>\n<p>&#8220;&#8230;Then came the genuinely counterintuitive bit. You might assume the fix would be to restore fission, get the scissors working again. Instead the researchers knocked out the fusion machinery too, both mitofusins, MFN1 and MFN2, on top of DRP1. With neither side of the cycle running, the mitochondria settled into a kind of frozen equilibrium the team calls mitochondrial stasis. And <span style=\"text-decoration: underline;\"><strong>these triple-knockout mice fared markedly better: less injury, less fibrosis, fewer tumours, whether the cancer arose spontaneously or was provoked by oncogenes<\/strong><\/span>. The cGAS-STING alarm, blaring in the DRP1-only mice, fell almost silent. <span style=\"text-decoration: underline;\"><strong>Delete the cGAS sensor directly and the tumours dwindled too, which <span style=\"color: #ff0000; text-decoration: underline;\">nails the inflammatory pathway to the cancer rather than leaving it a bystander<\/span><\/strong><\/span>. There was a metabolic tell, as well. The DRP1-deficient livers showed a <span style=\"text-decoration: underline;\"><strong>buildup of dihydroorotate and orotate, intermediates in the manufacture of pyrimidines, the raw nucleotides a cell needs to copy its DNA and keep dividing. Exactly the sort of supply line a growing tumour wants<\/strong><\/span>. In the stasis mice, that signal was blunted.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>One of the rare studies that quietly lets the truth out in the open. Namely, that cancer&#8230;<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[2],"tags":[55,383,1243,2249,12,61,77],"class_list":["post-3102","post","type-post","status-publish","format-standard","hentry","category-science","tag-cancer","tag-fao","tag-fission","tag-fusion","tag-inflammation","tag-liver","tag-mitochondria","wpcat-2-id"],"_links":{"self":[{"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/posts\/3102","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/haidut.me\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=3102"}],"version-history":[{"count":1,"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/posts\/3102\/revisions"}],"predecessor-version":[{"id":3103,"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/posts\/3102\/revisions\/3103"}],"wp:attachment":[{"href":"https:\/\/haidut.me\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=3102"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/haidut.me\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=3102"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/haidut.me\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=3102"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}