{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Goncalves RLS"],"funding":["NIDDK NIH HHS","NHLBI NIH HHS"],"pagination":["1057-1065"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12758653"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["643(8073)"],"pubmed_abstract":["Mitochondrial reactive oxygen species (mROS) are central to physiology<sup>1,2</sup>. Excess mROS production has been associated with several disease states<sup>2,3</sup>; however, the precise sources, regulation and mechanism of generation in vivo remain unclear, which limits translational efforts. Here we show that in obesity, hepatic coenzyme Q (CoQ) synthesis is impaired, which increases the CoQH<sub>2</sub> to CoQ (CoQH<sub>2</sub>/CoQ) ratio and drives excessive mROS production through reverse electron transport (RET) from site I<sub>Q</sub> in complex I. Using multiple complementary genetic and pharmacological models in vivo, we demonstrate that RET is crucial for metabolic health. In patients with steatosis, the hepatic CoQ biosynthetic program is also suppressed, and the CoQH<sub>"],"journal":["Nature"],"pubmed_title":["CoQ imbalance drives reverse electron transport to disrupt liver metabolism."],"pmcid":["PMC12758653"],"funding_grant_id":["R01 DK128168","R01 HL148137","R01 DK123458","P30 DK127984"],"pubmed_authors":["Riveros JK","Wang ZB","Goncalves RLS","Fu X","Rosique C","Parlakgul G","Graupera I","Lee GY","Burgess SC","Inouye KE","Hotamıslıgil GS","Hui ST","Saksi J","Coll M","Arruda AP"],"additional_accession":[]},"is_claimable":false,"name":"CoQ imbalance drives reverse electron transport to disrupt liver metabolism.","description":"Mitochondrial reactive oxygen species (mROS) are central to physiology<sup>1,2</sup>. Excess mROS production has been associated with several disease states<sup>2,3</sup>; however, the precise sources, regulation and mechanism of generation in vivo remain unclear, which limits translational efforts. Here we show that in obesity, hepatic coenzyme Q (CoQ) synthesis is impaired, which increases the CoQH<sub>2</sub> to CoQ (CoQH<sub>2</sub>/CoQ) ratio and drives excessive mROS production through reverse electron transport (RET) from site I<sub>Q</sub> in complex I. Using multiple complementary genetic and pharmacological models in vivo, we demonstrate that RET is crucial for metabolic health. In patients with steatosis, the hepatic CoQ biosynthetic program is also suppressed, and the CoQH<sub>","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jul","modification":"2026-06-06T10:30:42.214Z","creation":"2026-05-29T03:11:32.656Z"},"accession":"S-EPMC12758653","cross_references":{"pubmed":["40437093"],"doi":["10.1038/s41586-025-09072-1"]}}