2024-03-28T14:45:11Z
https://niigata-u.repo.nii.ac.jp/oai
oai:niigata-u.repo.nii.ac.jp:00034024
2022-12-15T04:04:20Z
453:455
471:561:562
ゲムシタビンはミトコンドリア常在性E3ユビキチンリガーゼMUL1を介してPINK1を安定化しParkin非依存性マイトファジーを誘導する
Gemcitabine induces Parkinindependent mitophagy through mitochondrial-resident E3 ligase MUL1-mediated stabilization of PINK1
Igarashi, Ryoko
178046
新潟大学
博士(医学)
Mitophagy plays an important role in the maintenance of mitochondrial homeostasis. PTEN-induced kinase (PINK1), a key regulator of mitophagy, is degraded constitutively under steady-state conditions. During mitophagy, it becomes stabilized in the outer mitochondrial membrane, particularly under mitochondrial stress conditions, such as in treatment with uncouplers, generation of excessive mitochondrial reactive oxygen species, and formation of protein aggregates in mitochondria. StabilizedPINK1 recruits and activates E3 ligases, such as Parkin and mitochondrial ubiquitin ligase (MUL1), to ubiquitinate mitochondrial proteins and induce ubiquitin-mediated mitophagy. Here, we found that the anticancer drug gemcitabine induces the stabilization of PINK1 and subsequent mitophagy, even in the absence of Parkin. We also found that gemcitabine-induced stabilization of PINK1 was not accompanied by mitochondrial depolarization. Interestingly, the stabilization of PINK1 was mediated by MUL1. These results suggest that gemcitabine induces mitophagy through MUL1-mediated stabilization of PINK1 on the mitochondrial membrane independently of mitochondrial depolarization.
Scientific Reports. 2020, 10, 1465
新大院博(医)甲第933号
thesis
2020-03-23
application/pdf
application/pdf
13101甲第4699号
https://niigata-u.repo.nii.ac.jp/record/34024/files/r1nmk933.pdf
https://niigata-u.repo.nii.ac.jp/record/34024/files/r1nmk933_a.pdf
eng
info:doi/10.1038/s41598-020-58315-w