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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Main Authors: Singhal, Neel S, Bai, Meirong, Lee, Evan M, Luo, Shuo, Cook, Kayleigh R, Ma, Dengke K
Format: Article in Journal/Newspaper
Language:unknown
Published: eScholarship, University of California 2020
Subjects:
Online Access:https://escholarship.org/uc/item/0vn932dh
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spelling ftcdlib:oai:escholarship.org/ark:/13030/qt0vn932dh 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 application/pdf https://escholarship.org/uc/item/0vn932dh unknown eScholarship, University of California qt0vn932dh https://escholarship.org/uc/item/0vn932dh public Arctic ground squirrel cell biology genetics genomics ischemic tolerance mitochondria Biochemistry and Cell Biology article 2020 ftcdlib 2021-01-24T17:37:54Z 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 University of California: eScholarship Arctic
institution Open Polar
collection University of California: eScholarship
op_collection_id ftcdlib
language unknown
topic Arctic ground squirrel
cell biology
genetics
genomics
ischemic tolerance
mitochondria
Biochemistry and Cell Biology
spellingShingle Arctic ground squirrel
cell biology
genetics
genomics
ischemic tolerance
mitochondria
Biochemistry and 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.
topic_facet Arctic ground squirrel
cell biology
genetics
genomics
ischemic tolerance
mitochondria
Biochemistry and 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 Article in Journal/Newspaper
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 eScholarship, University of California
publishDate 2020
url https://escholarship.org/uc/item/0vn932dh
geographic Arctic
geographic_facet Arctic
genre Arctic ground squirrel
Arctic
genre_facet Arctic ground squirrel
Arctic
op_relation qt0vn932dh
https://escholarship.org/uc/item/0vn932dh
op_rights public
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