Mitochondrial translation deficiency impairs NAD⁺ -mediated lysosomal acidification.

ABSTRACT: Mitochondrial translation dysfunction is associated with neurodegenerative and cardiovascular diseases. Cells eliminate defective mitochondria by the lysosomal machinery via autophagy. The relationship between mitochondrial translation and lysosomal function is unknown. In this study, mitochondrial translation-deficient hearts from p32-knockout mice were found to exhibit enlarged lysosomes containing lipofuscin, suggesting impaired lysosome and autolysosome function. These mice also displayed autophagic abnormalities, such as p62 accumulation and LC3 localization around broken mitochondria. The expression of genes encoding for nicotinamide adenine dinucleotide (NAD⁺ ) biosynthetic enzymes-Nmnat3 and Nampt-and NAD⁺ levels were decreased, suggesting that NAD⁺

SUBMITTER: Yagi M 

PROVIDER: S-EPMC8047443 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature