Effect of the mitochondrial unfolded protein response on hypoxic death and mitochondrial protein aggregation

• Published in: Cell death & disease Vol. 12; no. 7; p. 711
• Main Authors: Yan, Junyi, Sun, Chun-Ling, Shin, Seokyung, Van Gilst, Marc, Crowder, C. Michael
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15-07-2021; Springer Nature B.V; Nature Publishing Group
• Subjects: 13/44; 13/89; 14; 14/19; 14/35; 14/63; 38/47; 38/70; 42/41; 59/5; 631/80/642/333/1465; 631/80/82/2344; 64/11; Antibodies; Apoptosis; Biochemistry; Biomedical and Life Sciences; Cell activation; Cell Biology; Cell Culture; Cell death; Hypoxia; Immunology; Life Sciences; Mitochondria; Protein folding; Protein interaction; Proteins
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-021-03979-z

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 (UPR
mt
) 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 UPR
mt
to determine the relationship between hypoxic cell death, UPR
mt
activation, and hypoxia-induced mitochondrial protein aggregation (HIMPA). We find that resistance to hypoxic cell death invariantly mitigated HIMPA. We also find that UPR
mt
activation invariantly mitigated HIMPA. However, UPR
mt
activation was neither necessary nor sufficient for resistance to hypoxic death and vice versa. We conclude that UPR
mt
is not necessarily hypoxia protective against cell death but does protect from mitochondrial protein aggregation, one of the early hypoxic pathologies in
C. elegans
.