biostudies-literatureUnknown27(5)Miki KJSPSLysosomes, the hub of metabolic signaling, are associated with various diseases and participate in autophagy by supplying nutrients to cells under nutrient starvation. However, their function and regulation under glucose starvation remain unclear and are studied herein. Under glucose starvation, lysosomal protein expression decreased, leading to the accumulation of damaged lysosomes. Subsequently, cell death occurred via ferroptosis and iron accumulation due to DMT1 degradation. GPX4, a key factor in ferroptosis inhibition located on the outer membrane of lysosomes, accumulated in lysosomes, especially under glucose starvation, to protect cells from ferroptosis. ALDOA, GAPDH, NAMPT, and PGK1 are also located on the outer membrane of lysosomes and participate in lysosomal function. These eniScience109735https://www.ebi.ac.uk/biostudies/studies/S-EPMC11067335biostudies-literatureGlucose starvation causes ferroptosis-mediated lysosomal dysfunction.PMC11067335Yagi MUchiumi TYoshimoto KKang DKunisaki YMiki KfalseGlucose starvation causes ferroptosis-mediated lysosomal dysfunction.Lysosomes, the hub of metabolic signaling, are associated with various diseases and participate in autophagy by supplying nutrients to cells under nutrient starvation. However, their function and regulation under glucose starvation remain unclear and are studied herein. Under glucose starvation, lysosomal protein expression decreased, leading to the accumulation of damaged lysosomes. Subsequently, cell death occurred via ferroptosis and iron accumulation due to DMT1 degradation. GPX4, a key factor in ferroptosis inhibition located on the outer membrane of lysosomes, accumulated in lysosomes, especially under glucose starvation, to protect cells from ferroptosis. ALDOA, GAPDH, NAMPT, and PGK1 are also located on the outer membrane of lysosomes and participate in lysosomal function. These en2024-01-01T00:00:00Z2024 May2026-07-15T04:50:38.767Z2026-06-29T03:09:55.904ZS-EPMC110673353870684310.1016/j.isci.2024.109735