biostudies-literatureUnknown4(1)Cho YLGlucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme in the pentose phosphate pathway (PPP) in glycolysis. Glucose metabolism is closely implicated in the regulation of mitophagy, a selective form of autophagy for the degradation of damaged mitochondria. The PPP and its key enzymes such as G6PD possess important metabolic functions, including biosynthesis and maintenance of intracellular redox balance, while their implication in mitophagy is largely unknown. Here, via a whole-genome CRISPR-Cas9 screening, we identified that G6PD regulates PINK1 (phosphatase and tensin homolog [PTEN]-induced kinase 1)-Parkin-mediated mitophagy. The function of G6PD in mitophagy was verified via multiple approaches. G6PD deletion significantly inhibited mitophagy, which can be rescued by G6PDLife metabolismloae040https://www.ebi.ac.uk/biostudies/studies/S-EPMC11749863biostudies-literatureGlucose-6-phosphate dehydrogenase regulates mitophagy by maintaining PINK1 stability.PMC11749863Yang JLim NSYBay BHKuah BZMCho YLLing SCShen HMTan HWSFu NfalseGlucose-6-phosphate dehydrogenase regulates mitophagy by maintaining PINK1 stability.Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme in the pentose phosphate pathway (PPP) in glycolysis. Glucose metabolism is closely implicated in the regulation of mitophagy, a selective form of autophagy for the degradation of damaged mitochondria. The PPP and its key enzymes such as G6PD possess important metabolic functions, including biosynthesis and maintenance of intracellular redox balance, while their implication in mitophagy is largely unknown. Here, via a whole-genome CRISPR-Cas9 screening, we identified that G6PD regulates PINK1 (phosphatase and tensin homolog [PTEN]-induced kinase 1)-Parkin-mediated mitophagy. The function of G6PD in mitophagy was verified via multiple approaches. G6PD deletion significantly inhibited mitophagy, which can be rescued by G6PD2025-01-01T00:00:00Z2025 Feb2025-04-05T11:34:18.373Z2025-04-05T11:34:18.373ZS-EPMC117498633987298410.1093/lifemeta/loae040