| RRC ID |
72665
|
| 著者 |
Miyazaki N, Shiratori R, Oshima T, Zhang Z, Valencia R, Kranrod J, Fang L, Seubert JM, Ito K, Aoki S.
|
| タイトル |
PINK1-dependent and Parkin-independent mitophagy is involved in reprogramming of glycometabolism in pancreatic cancer cells.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
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 suppression in pancreatic cancer cells, intracellular glycometabolism is shifted toward mitochondrial oxidative phosphorylation in an autophagy-dependent manner for cellular survival. Here, we hypothesized that mitophagy, which selectively degrades mitochondria via autophagy, is involved in mitochondrial 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.
|
| 巻・号 |
625
|
| ページ |
167-173
|
| 公開日 |
2022-10-15
|
| DOI |
10.1016/j.bbrc.2022.08.004
|
| PII |
S0006-291X(22)01109-3
|
| PMID |
35963163
|
| MeSH |
Humans
Mitophagy*
Pancreatic Neoplasms*
Protein Kinases* / genetics
Protein Kinases* / metabolism
Ubiquitin / metabolism
Ubiquitin-Protein Ligases / genetics
Ubiquitin-Protein Ligases / metabolism
|
| IF |
2.985
|
| リソース情報 |
| ヒト・動物細胞 |
PANC-1(RCB2095) |
