Control of NAD⁺ homeostasis by autophagic flux modulates mitochondrial and cardiac function.

ABSTRACT: Impaired autophagy is known to cause mitochondrial dysfunction and heart failure, in part due to altered mitophagy and protein quality control. However, whether additional mechanisms are involved in the development of mitochondrial dysfunction and heart failure in the setting of deficient autophagic flux remains poorly explored. Here, we show that impaired autophagic flux reduces nicotinamide adenine dinucleotide (NAD⁺) availability in cardiomyocytes. NAD⁺ deficiency upon autophagic impairment is attributable to the induction of nicotinamide N-methyltransferase (NNMT), which methylates the NAD⁺ precursor nicotinamide (NAM) to generate N-methyl-nicotinamide (MeNAM). The administration of nicotinamide mononucleotide (NMN) or inhibition of NNMT activity in aut

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC10897141 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature