Silencing GGH induces autophagy by increasing folate stress and production of NADH.

ABSTRACT: There is an inextricable link between metabolic disorders and autophagy. Gamma-glutamyl hydrolase (GGH) is a lysosomal glycoprotein that reduces intracellular folate stress by catalyzing the hydrolysis of polyglutamylated folate into transportable monoglutamate. The relationship between folate metabolism, involving the folate metabolic enzyme GGH, and autophagy has rarely been reported. In this study, we found that GGH functions as a crucial oncogene in lung adenocarcinomas. Importantly, we found that cell autophagy and autophagic cell death are induced by GGH silencing through the elevated folate stress resulting from folate metabolism and the folate metabolite nicotinamide adenine dinucleotide (NADH). By increasing the NADH/NAD+ ratio, silencing GGH activates adenosine monophosphate-acti

SUBMITTER: Li Y 

PROVIDER: S-EPMC12527274 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature