期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 625, 期 -, 页码 167-173出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2022.08.004
关键词
Mitophagy; PINK1; Parkin; Pancreatic cancer; Glycometabolism
资金
- JSPS KAKENHI [19K16440, 19KK0399]
- National Sciences and Engineering Research Council of Canada (NSERC) [RGPIN-2018-05696]
- Uehara Memorial Foundation
- Yasuda Medical Foundation
Cancer cells rely on glycolysis to generate ATP for survival, but metabolic reprogramming involves mitophagy in mitochondrial activation, providing a potential strategy for cancer therapy.
Cancer cells rely on glycolysis to generate ATP for survival. However, inhibiting glycolysis is insufficient for the eradication of cancer cells because glycolysis-suppressed cells undergo metabolic reprogramming toward mitochondrial oxidative phosphorylation. We previously described that upon glycolytic sup-pression in pancreatic cancer cells, intracellular glycometabolism is shifted toward mitochondrial oxidative phosphorylation in an autophagy-dependent manner for cellular survival. Here, we hypothe-sized that mitophagy, which selectively degrades mitochondria via autophagy, is involved in mito-chondrial activation under metabolic reprogramming. We revealed that glycolytic suppression notably increased mitochondrial membrane potential and mitophagy in a pancreatic cancer cell model (PANC-1). PTEN-induced kinase 1 (PINK1), a ubiquitin kinase that regulates mitophagy in healthy cells, regulated mitochondrial activation through mitophagy by glycolytic suppression. However, Parkin, a ubiquitin ligase regulated by PINK1 in healthy cells to induce mitophagy, was not involved in the PINK1-dependent mitophagy of the cancer glycometabolism. These results imply that cancer cells and healthy cells have different regulatory pieces of machinery for mitophagy, and inhibition of cancer-specific mechanisms may be a potential strategy for cancer therapy targeting metabolic reprogramming.(c) 2022 Elsevier Inc. All rights reserved.
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