RRC ID 80831
Author Sun CL, Van Gilst M, Crowder CM.
Title Hypoxia-induced mitochondrial stress granules.
Journal Cell Death Dis
Abstract Perturbations of mitochondrial proteostasis have been associated with aging, neurodegenerative diseases, and recently with hypoxic injury. While examining hypoxia-induced mitochondrial protein aggregation in C. elegans, we found that sublethal hypoxia, sodium azide, or heat shock-induced abundant ethidium bromide staining mitochondrial granules that preceded evidence of protein aggregation. Genetic manipulations that reduce cellular and organismal hypoxic death block the formation of these mitochondrial stress granules (mitoSG). Knockdown of mitochondrial nucleoid proteins also blocked the formation of mitoSG by a mechanism distinct from the mitochondrial unfolded protein response. Lack of the major mitochondrial matrix protease LONP-1 resulted in the constitutive formation of mitoSG without external stress. Ethidium bromide-staining RNA-containing mitochondrial granules were also observed in rat cardiomyocytes treated with sodium azide, a hypoxia mimetic. Mitochondrial stress granules are an early mitochondrial pathology controlled by LONP and the nucleoid, preceding hypoxia-induced protein aggregation.
Volume 14(7)
Pages 448
Published 2023-7-19
DOI 10.1038/s41419-023-05988-6
PII 10.1038/s41419-023-05988-6
PMID 37468471
PMC PMC10356818
MeSH Animals Caenorhabditis elegans* / metabolism Ethidium / metabolism Hypoxia / metabolism Mitochondrial Proteins / genetics Mitochondrial Proteins / metabolism Protein Aggregates* Rats Sodium Azide Stress Granules
Resource
C.elegans tm6212 tm3586 tm5171 tm4919