| RRC ID |
86614
|
| 著者 |
Sone M, Mitsuhashi N, Sugiura Y, Matsuoka Y, Maeda R, Yamauchi A, Okahashi R, Yamashita J, Sone K, Enju S, Anegawa D, Yamaguchi Y.
|
| タイトル |
Identification of genes supporting cold resistance of mammalian cells: lessons from a hibernator.
|
| ジャーナル |
Cell Death Dis
|
| Abstract |
Susceptibility of human cells to cold stress restricts the use of therapeutic hypothermia and long-term preservation of organs at low temperatures. In contrast, cells of mammalian hibernators possess remarkable cold resistance, but little is known about the molecular mechanisms underlying this phenomenon. In this study, we conducted a gain-of-function screening of genes that confer cold resistance to cold-vulnerable human cells using a cDNA library constructed from the Syrian hamster, a mammalian hibernator, and identified Gpx4 as a potent suppressor of cold-induced cell death. Additionally, genetic deletion of or pharmacological inhibition of Gpx4 revealed that Gpx4 is necessary for suppressing lipid peroxidation specifically under cold in hamster cell lines. Genetic disruption of other ferroptosis-suppressing pathways, namely biopterin synthesis and mitochondrial or plasma membrane CoQ reduction pathways, also accelerated cold-induced cell death under Gpx4 dysfunction. Collectively, ferroptosis-suppressing pathways protect the cells of a mammalian hibernator from cold-induced cell death and the augmentation of these pathways renders cold resistance to cells of non-hibernators, including humans.
|
| 巻・号 |
15(9)
|
| ページ |
685
|
| 公開日 |
2024-9-19
|
| DOI |
10.1038/s41419-024-07059-w
|
| PII |
10.1038/s41419-024-07059-w
|
| PMID |
39300059
|
| PMC |
PMC11413375
|
| MeSH |
Animals
Cell Death
Cell Line
Cold Temperature*
Cricetinae
Ferroptosis / genetics
Hibernation* / genetics
Humans
Lipid Peroxidation*
Mesocricetus
Mitochondria / genetics
Mitochondria / metabolism
Phospholipid Hydroperoxide Glutathione Peroxidase* / genetics
Phospholipid Hydroperoxide Glutathione Peroxidase* / metabolism
Ubiquinone / analogs & derivatives
Ubiquinone / metabolism
Ubiquinone / pharmacology
|
| IF |
6.304
|
| リソース情報 |
| 遺伝子材料 |
pCMV-VSV-G (RDB04392) |
