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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ftpubmed:oai:pubmedcentral.nih.gov:7671683 2023-05-15T14:31:28+02:00 Cytoprotection by a naturally occurring variant of ATP5G1 in Arctic ground squirrel neural progenitor cells Singhal, Neel S Bai, Meirong Lee, Evan M Luo, Shuo Cook, Kayleigh R Ma, Dengke K 2020-10-14 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671683/ http://www.ncbi.nlm.nih.gov/pubmed/33050999 https://doi.org/10.7554/eLife.55578 en eng eLife Sciences Publications, Ltd http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671683/ http://www.ncbi.nlm.nih.gov/pubmed/33050999 http://dx.doi.org/10.7554/eLife.55578 © 2020, Singhal et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. CC-BY eLife Cell Biology Text 2020 ftpubmed https://doi.org/10.7554/eLife.55578 2020-11-22T01:44:03Z 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. Text Arctic ground squirrel Arctic PubMed Central (PMC) Arctic eLife 9 |
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Cell Biology |
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Cell Biology Singhal, Neel S Bai, Meirong Lee, Evan M Luo, Shuo Cook, Kayleigh R Ma, Dengke K Cytoprotection by a naturally occurring variant of ATP5G1 in Arctic ground squirrel neural progenitor cells |
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Cell Biology |
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 |
Text |
author |
Singhal, Neel S Bai, Meirong Lee, Evan M Luo, Shuo Cook, Kayleigh R Ma, Dengke K |
author_facet |
Singhal, Neel S Bai, Meirong Lee, Evan M Luo, Shuo Cook, Kayleigh R Ma, Dengke K |
author_sort |
Singhal, Neel S |
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 |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671683/ http://www.ncbi.nlm.nih.gov/pubmed/33050999 https://doi.org/10.7554/eLife.55578 |
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Arctic |
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Arctic |
genre |
Arctic ground squirrel Arctic |
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Arctic ground squirrel Arctic |
op_source |
eLife |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671683/ http://www.ncbi.nlm.nih.gov/pubmed/33050999 http://dx.doi.org/10.7554/eLife.55578 |
op_rights |
© 2020, Singhal et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
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CC-BY |
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https://doi.org/10.7554/eLife.55578 |
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eLife |
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9 |
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1766305087139872768 |