Selective NADH communication from α-ketoglutarate dehydrogenase to mitochondrial transhydrogenase prevents reactive oxygen species formation under reducing conditions in the heart.

ABSTRACT: In heart failure, a functional block of complex I of the respiratory chain provokes superoxide generation, which is transformed to H₂O₂ by dismutation. The Krebs cycle produces NADH, which delivers electrons to complex I, and NADPH for H₂O₂ elimination via isocitrate dehydrogenase and nicotinamide nucleotide transhydrogenase (NNT). At high NADH levels, α-ketoglutarate dehydrogenase (α-KGDH) is a major source of superoxide in skeletal muscle mitochondria with low NNT activity. Here, we analyzed how α-KGDH and NNT control H₂O₂ emission in cardiac mitochondria. In cardiac mitochondria from NNT-competent BL/6N mice, H₂O₂ emission is equally low with pyruvate/malate (P/M) or α-ketoglutarate (α-KG) as substra

SUBMITTER: Wagner M 

PROVIDER: S-EPMC7399685 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature