ALKBH7 mediates necrosis via rewiring of glyoxal metabolism.

ABSTRACT: Alkb homolog 7 (ALKBH7) is a mitochondrial α-ketoglutarate dioxygenase required for DNA alkylation-induced necrosis, but its function and substrates remain unclear. Herein, we show ALKBH7 regulates dialdehyde metabolism, which impacts the cardiac response to ischemia-reperfusion (IR) injury. Using a multi-omics approach, we find no evidence ALKBH7 functions as a prolyl-hydroxylase, but we do find Alkbh7^-/- mice have elevated glyoxalase I (GLO-1), a dialdehyde detoxifying enzyme. Metabolic pathways related to the glycolytic by-product methylglyoxal (MGO) are rewired in Alkbh7^-/- mice, along with elevated levels of MGO protein adducts. Despite greater glycative stress, hearts from Alkbh7^-/- mice are protected against IR injury, in a manne

SUBMITTER: Kulkarni CA 

PROVIDER: S-EPMC7442491 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature