SIRT5-mediated deacetylation of LDHB promotes autophagy and tumorigenesis in colorectal cancer.

ABSTRACT: Lactate dehydrogenase B (LDHB) is a glycolytic enzyme that catalyses the conversion of lactate and NAD⁺ to pyruvate, NADH and H⁺ . Protons (H⁺ ) generated by LDHB promote lysosomal acidification and autophagy in cancer, but how this role is regulated has not been defined. In this study, we identified an important post-translational mechanism by which LDHB is regulated during autophagy in cancer cells. Mass spectrometry revealed that protein sirtuin 5 (SIRT5) is a binding partner of LDHB that deacetylated LDHB at lysine-329, thereby promoting its enzymatic activity. Deacetylated LDHB increased autophagy and accelerated the growth of colorectal cancer (CRC) cells. Notably, SIRT5 knockout or inhibition by GW5074 increased LDHB acetylation at K329 and inhibited

SUBMITTER: Shi L 

PROVIDER: S-EPMC6360364 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature