Data for: Cytoprotection by a naturally occurring variant of ATP5G1 in Arctic ground squirrel neural progenitor cells

• Main Authors: Singhal, Neel, Ma, Dengke
• Format: Dataset
• Language: unknown
• Published: 2020
• Subjects: Arctic; Arctic ground squirrel
• Online Access: https://zenodo.org/record/4086121; https://doi.org/10.7272/Q6MW2FCP

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. Funding provided by: American Heart AssociationCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000968Award Number: 18CDA3403044Funding provided by: National Institute of General Medical SciencesCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000057Award Number: 5R01GM117461-04Funding provided by: Innovative Genomics InstituteCrossref Funder Registry ID: http://dx.doi.org/10.13039/100014220Award Number: A132317 Contains 2 files: 1) Source data for manuscript figures in Prism format (see methods and figure legends for details) 2) Survival screen gene set in excel format from sequenced plasmids (see methods for details)