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Updated: Jun 27, 2025
04:01
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
945
Glucose starvation causes ferroptosis-mediated lysosomal dysfunction
Kenji Miki1,2, Mikako Yagi1,3, Dongchon Kang1,4,5
1Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
Iscience
|May 6, 2024
Summary
Glucose starvation causes lysosomal dysfunction and ferroptosis by decreasing protein expression and damaging lysosomes. This leads to iron accumulation and cell death, despite GPX4 accumulation for protection.
Area of Science:
- Cell Biology
- Metabolic Signaling
- Disease Mechanisms
Background:
- Lysosomes are central to metabolic signaling and autophagy, supplying nutrients during starvation.
- Lysosome function and regulation under glucose starvation are not well understood.
Purpose of the Study:
- To investigate lysosome function and regulation during glucose starvation.
- To elucidate the mechanisms of cell death under glucose starvation.
Main Methods:
- Analysis of lysosomal protein expression under glucose starvation.
- Assessment of lysosome damage and cell death pathways (ferroptosis).
- Investigation of key proteins like GPX4, ALDOA, GAPDH, NAMPT, and PGK1 localization and function.
Main Results:
- Glucose starvation decreased lysosomal protein expression, causing lysosome damage.
- Cell death occurred via ferroptosis, linked to DMT1 degradation and iron accumulation.
- GPX4 accumulated in lysosomes for ferroptosis protection, while key enzymes (ALDOA, GAPDH, NAMPT, PGK1) showed reduced function.
Conclusions:
- Lysosomal dysfunction and ferroptosis are key outcomes of glucose starvation.
- Impaired lysosomal enzyme function contributes to cell death under glucose deprivation.
- Understanding these mechanisms may offer new therapeutic strategies for lysosomal diseases.
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