Cytoprotection by a naturally occurring variant of ATP5G1 in Arctic ground squirrel neural progenitor cells
Many organisms in nature have evolved mechanisms to tolerate severe hypoxia or ischemia, including the hibernation-capable Arctic ground squirrel (AGS). Although hypoxic or ischemia tolerance in AGS involves physiological adaptations, little is known about the critical cellular mechanisms underlying...
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ftdoajarticles:oai:doaj.org/article:4789a85a74c64746853557a86d853cdd 2023-05-15T14:31:28+02:00 Cytoprotection by a naturally occurring variant of ATP5G1 in Arctic ground squirrel neural progenitor cells Neel S Singhal Meirong Bai Evan M Lee Shuo Luo Kayleigh R Cook Dengke K Ma 2020-10-01T00:00:00Z https://doi.org/10.7554/eLife.55578 https://doaj.org/article/4789a85a74c64746853557a86d853cdd EN eng eLife Sciences Publications Ltd https://elifesciences.org/articles/55578 https://doaj.org/toc/2050-084X doi:10.7554/eLife.55578 2050-084X e55578 https://doaj.org/article/4789a85a74c64746853557a86d853cdd eLife, Vol 9 (2020) Arctic ground squirrel ischemic tolerance mitochondria Medicine R Science Q Biology (General) QH301-705.5 article 2020 ftdoajarticles https://doi.org/10.7554/eLife.55578 2022-12-31T00:03:08Z Many organisms in nature have evolved mechanisms to tolerate severe hypoxia or ischemia, including the hibernation-capable Arctic ground squirrel (AGS). Although hypoxic or ischemia tolerance in AGS involves physiological adaptations, little is known about the critical cellular mechanisms underlying intrinsic AGS cell resilience to metabolic stress. Through cell survival-based cDNA expression screens in neural progenitor cells, we identify a genetic variant of AGS Atp5g1 that confers cell resilience to metabolic stress. Atp5g1 encodes a subunit of the mitochondrial ATP synthase. Ectopic expression in mouse cells and CRISPR/Cas9 base editing of endogenous AGS loci revealed causal roles of one AGS-specific amino acid substitution in mediating cytoprotection by AGS ATP5G1. AGS ATP5G1 promotes metabolic stress resilience by modulating mitochondrial morphological change and metabolic functions. Our results identify a naturally occurring variant of ATP5G1 from a mammalian hibernator that critically contributes to intrinsic cytoprotection against metabolic stress. Article in Journal/Newspaper Arctic ground squirrel Arctic Directory of Open Access Journals: DOAJ Articles Arctic eLife 9 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
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Arctic ground squirrel ischemic tolerance mitochondria Medicine R Science Q Biology (General) QH301-705.5 |
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Arctic ground squirrel ischemic tolerance mitochondria Medicine R Science Q Biology (General) QH301-705.5 Neel S Singhal Meirong Bai Evan M Lee Shuo Luo Kayleigh R Cook Dengke K Ma Cytoprotection by a naturally occurring variant of ATP5G1 in Arctic ground squirrel neural progenitor cells |
topic_facet |
Arctic ground squirrel ischemic tolerance mitochondria Medicine R Science Q Biology (General) QH301-705.5 |
description |
Many organisms in nature have evolved mechanisms to tolerate severe hypoxia or ischemia, including the hibernation-capable Arctic ground squirrel (AGS). Although hypoxic or ischemia tolerance in AGS involves physiological adaptations, little is known about the critical cellular mechanisms underlying intrinsic AGS cell resilience to metabolic stress. Through cell survival-based cDNA expression screens in neural progenitor cells, we identify a genetic variant of AGS Atp5g1 that confers cell resilience to metabolic stress. Atp5g1 encodes a subunit of the mitochondrial ATP synthase. Ectopic expression in mouse cells and CRISPR/Cas9 base editing of endogenous AGS loci revealed causal roles of one AGS-specific amino acid substitution in mediating cytoprotection by AGS ATP5G1. AGS ATP5G1 promotes metabolic stress resilience by modulating mitochondrial morphological change and metabolic functions. Our results identify a naturally occurring variant of ATP5G1 from a mammalian hibernator that critically contributes to intrinsic cytoprotection against metabolic stress. |
format |
Article in Journal/Newspaper |
author |
Neel S Singhal Meirong Bai Evan M Lee Shuo Luo Kayleigh R Cook Dengke K Ma |
author_facet |
Neel S Singhal Meirong Bai Evan M Lee Shuo Luo Kayleigh R Cook Dengke K Ma |
author_sort |
Neel S Singhal |
title |
Cytoprotection by a naturally occurring variant of ATP5G1 in Arctic ground squirrel neural progenitor cells |
title_short |
Cytoprotection by a naturally occurring variant of ATP5G1 in Arctic ground squirrel neural progenitor cells |
title_full |
Cytoprotection by a naturally occurring variant of ATP5G1 in Arctic ground squirrel neural progenitor cells |
title_fullStr |
Cytoprotection by a naturally occurring variant of ATP5G1 in Arctic ground squirrel neural progenitor cells |
title_full_unstemmed |
Cytoprotection by a naturally occurring variant of ATP5G1 in Arctic ground squirrel neural progenitor cells |
title_sort |
cytoprotection by a naturally occurring variant of atp5g1 in arctic ground squirrel neural progenitor cells |
publisher |
eLife Sciences Publications Ltd |
publishDate |
2020 |
url |
https://doi.org/10.7554/eLife.55578 https://doaj.org/article/4789a85a74c64746853557a86d853cdd |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic ground squirrel Arctic |
genre_facet |
Arctic ground squirrel Arctic |
op_source |
eLife, Vol 9 (2020) |
op_relation |
https://elifesciences.org/articles/55578 https://doaj.org/toc/2050-084X doi:10.7554/eLife.55578 2050-084X e55578 https://doaj.org/article/4789a85a74c64746853557a86d853cdd |
op_doi |
https://doi.org/10.7554/eLife.55578 |
container_title |
eLife |
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9 |
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1766305084451323904 |