Mitochondrial superoxide targets energy metabolism to modulate epigenetic regulation of NRF2-mediated transcription.

ABSTRACT: Mitochondria are central to the metabolic circuitry that generates superoxide radicals/anions (O₂^•-) as a by-product of oxygen metabolism. By regulating superoxide levels, manganese superoxide dismutase plays important roles in numerous biochemical and molecular events essential for the survival of aerobic life. In this study, we used MitoParaquat (mPQ) to generate mitochondria-specific O₂^•- and stable isotope-resolved metabolomics tracing in primary human epidermal keratinocytes to investigate how O₂^•- generated in mitochondria regulates gene expression. The results reveal that isocitrate is blocked from conversion to α-ketoglutarate and that acetyl-coenzyme A (CoA) accumulates, which is consistent with a reduction in oxyge

SUBMITTER: Dhar SK 

PROVIDER: S-EPMC8765599 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature