Archive · 2026-W43

Mito.news 2026-W43

5 articles. Each URL is the original /articles/{id} path.

• biorxiv2026-10-20score 94

  GLP-1 receptor agonists plus vorasidenib make peroxynitrite that kills mutant IDH glioma

  Taglang, Viswanath and colleagues show that glucagon-like peptide-1 receptor (GLP1R) agonists synergize with the mutant isocitrate dehydrogenase inhibitor vorasidenib in patient-derived and murine mutant IDH glioma. GLP1R agonists raise cyclic AMP and protein kinase A, then nitric oxide synthase 1-dependent nitric oxide. That NO S-nitrosylates aconitase and ribonucleotide reductase, which stalls the tricarboxylic acid cycle and DNA synthesis (cytostatic). Vorasidenib relieves D-2-hydroxyglutarate suppression of pyruvate dehydrogenase, raising mitochondrial superoxide without killing on its own. Together, NO and superoxide form peroxynitrite, which damages lipids and DNA and drives apoptosis. The named redox convergence is nitric oxide plus superoxide to peroxynitrite. Aconitase is the metal-site enzyme they inhibit by S-nitrosylation. They do not report 4Fe to 3Fe cluster conversion.

• biorxiv2026-10-06score 93

  Mitoferrin-2 (SLC25A28) is synthetic lethal with nucleotide excision repair loss

  Yang, Hoeg, Durocher, Mouw, Offit, Lipkin and colleagues rank SLC25A28 as the top CRISPR hit that kills ERCC4-null bladder-cancer cells while sparing isogenic NER-proficient cells. SLC25A28 is mitoferrin-2, the mitochondrial inner-membrane carrier that imports ferrous iron for heme and iron-sulfur cofactor assembly. Loss of the carrier raises intracellular reactive oxygen species and DNA-damage signatures, which NER-deficient cells cannot clear. The authors do not report a named Fe-S nuclearity. The metal site in play is the mitochondrial Fe2+ import step, not a counted [2Fe-2S] or [4Fe-4S] enzyme.

• biorxiv2026-10-11score 90

  Frataxin-deficient autonomic neurons fire five-fold more spikes, raise mitochondrial ROS, and de-repress MEG3

  Lees, Zhang, Dottori, Napierala and colleagues show that hyperexcitability is a cell-autonomous property of human Friedreich ataxia autonomic neurons, not only a downstream consequence of dying heart or gut tissue. Frataxin is the mitochondrial iron-delivery protein for iron-sulfur cluster assembly. The cultures keep low FXN mRNA and protein, raise mitochondrial reactive oxygen species, shift from networked to tubular mitochondria, and die more. The authors do not report cluster nuclearity, so the bioinorganic frame is frataxin loss and mitochondrial oxidant load, not a measured [2Fe-2S] or [4Fe-4S] occupancy.

• biorxiv2026-10-09score 88

  Sub-toxic iron sulfate depolarizes neuroblastoma mitochondria, raises proton leak, and cuts hydrogen peroxide

  Mendonça, Rossignol, Amoedo, Oliveira and colleagues loaded SH-SY5Y neuroblastoma cells with 100 µM iron sulfate for 24 hours, a pulse that was not cytotoxic. Intracellular iron rose about four-fold. Mitochondria fragmented and lost membrane potential, yet mitochondrial content and OXPHOS coupling efficiency held. The only respiratory state that increased was proton leak. Total cellular oxidants and hydrogen peroxide output fell, ferritin rose, and the cells proliferated more while migrating less. The redox story is a leak-dependent drop in driving force that biophysically limits oxidant production, not a Fenton burst. The metal is loaded iron, stored in ferritin. Cluster nuclearity was not measured.

• biorxiv2026-10-21score 84

  Mitochondria-targeted OGG1 remaps alveolar transitional states after chlorine injures mtDNA

  Dubey, Crossman and Matalon follow chlorine inhalation with a mitochondria-targeted 8-oxoguanine DNA glycosylase-1 fusion (mOGG1) and, at 24 hours, single-nucleus RNA sequencing of mouse lung. They previously showed that oxidative mitochondrial DNA damage drives chlorine lung injury and that post-exposure mOGG1 improves survival. This preprint asks which epithelial and immune states carry that effect. Chlorine expands heterogeneous alveolar transitional programs, including a Krt8+ damage-associated state, and complicates interleukin-1 ligand-receptor traffic among neutrophils, macrophages, and epithelium. mOGG1 does not globally silence that network. It redistributes who talks to whom, including selected transitional populations. The named chemistry is 8-oxoguanine on mtDNA, the base-excision lesion of oxidative guanine. No Fe-S nuclearity is claimed.