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Physiological levels of formate activate mitochondrial superoxide/hydrogen peroxide release from mouse liver mitochondria
Author(s) -
Young Adrian,
Gardiner Danielle,
Brosnan Margaret E.,
Brosnan John T.,
Mailloux Ryan J.
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12777
Subject(s) - sodium formate , formate , chemistry , superoxide , hydrogen peroxide , mitochondrion , biochemistry , formate dehydrogenase , pyruvate dehydrogenase complex , cytochrome c oxidase , catalase , metabolite , metabolism , enzyme , inorganic chemistry , catalysis
Here, we found that formate, an essential one‐carbon metabolite, activates superoxide ( O 2 · − )/hydrogen peroxide (H 2 O 2 ) release from mitochondria. Sodium formate (30 μ m ) induces a significant increase in O 2 · − /H 2 O 2 production in liver mitochondria metabolizing pyruvate (50 μ m ). At concentrations deemed to be toxic, formate does not increase O 2 · − /H 2 O 2 production further. It was observed that the formate‐mediated increase in O 2 · − /H 2 O 2 production is not associated with cytochrome c oxidase ( COX ) inhibition or changes in membrane potential and NAD (P)H levels. Sodium formate supplementation increases phosphorylating respiration without altering proton leaks. Finally, it was observed that the 2‐oxoglutarate dehydrogenase ( OGDH ) inhibitors 3‐methyl‐2‐oxovaleric acid ( KMV ) and CPI ‐613 inhibit the formate‐induced increase in pyruvate‐driven ROS production. The importance of these findings in one‐carbon metabolism and physiology are discussed herein.