Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan; Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan
Mikako Yagi
Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan; Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan
Dongchon Kang
Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan; Kashiigaoka Rehabilitation Hospital, Fukuoka 813-0002, Japan; Department of Medical Laboratory Science, Faculty of Health Sciences, Junshin Gakuen University, Fukuoka 815-8510, Japan
Yuya Kunisaki
Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan
Koji Yoshimoto
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan
Takeshi Uchiumi
Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan; Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan; Corresponding author
Summary: 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 enzymes did not function effectively under glucose starvation, leading to lysosomal dysfunction and ferroptosis. These findings may facilitate the treatment of lysosomal-related diseases.
