RRC ID 76096
Author Yan J, Sun CL, Shin S, Van Gilst M, Crowder CM.
Title Effect of the mitochondrial unfolded protein response on hypoxic death and mitochondrial protein aggregation.
Journal Cell Death Dis
Abstract Mitochondria are the main oxygen consumers in cells and as such are the primary organelle affected by hypoxia. All hypoxia pathology presumably derives from the initial mitochondrial dysfunction. An early event in hypoxic pathology in C. elegans is disruption of mitochondrial proteostasis with induction of the mitochondrial unfolded protein response (UPRmt) and mitochondrial protein aggregation. Here in C. elegans, we screen through RNAis and mutants that confer either strong resistance to hypoxic cell death or strong induction of the UPRmt to determine the relationship between hypoxic cell death, UPRmt activation, and hypoxia-induced mitochondrial protein aggregation (HIMPA). We find that resistance to hypoxic cell death invariantly mitigated HIMPA. We also find that UPRmt activation invariantly mitigated HIMPA. However, UPRmt activation was neither necessary nor sufficient for resistance to hypoxic death and vice versa. We conclude that UPRmt is not necessarily hypoxia protective against cell death but does protect from mitochondrial protein aggregation, one of the early hypoxic pathologies in C. elegans.
Volume 12(7)
Pages 711
Published 2021-7-15
DOI 10.1038/s41419-021-03979-z
PII 10.1038/s41419-021-03979-z
PMID 34267182
PMC PMC8282665
MeSH Animals Animals, Genetically Modified Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Hypoxia Mitochondria / genetics Mitochondria / metabolism* Mitochondria / pathology Mitochondrial Proteins / genetics Mitochondrial Proteins / metabolism* Protein Aggregates Protein Aggregation, Pathological Unfolded Protein Response*
Resource
C.elegans tm4919