In:
PLOS Biology, Public Library of Science (PLoS), Vol. 19, No. 7 ( 2021-7-12), p. e3001302-
Abstract:
Defects in mitochondrial function activate compensatory responses in the cell. Mitochondrial stress that is caused by unfolded proteins inside the organelle induces a transcriptional response (termed the “mitochondrial unfolded protein response” [UPRmt]) that is mediated by activating transcription factor associated with stress 1 (ATFS-1). The UPRmt increases mitochondrial protein quality control. Mitochondrial dysfunction frequently causes defects in the import of proteins, resulting in the accumulation of mitochondrial proteins outside the organelle. In yeast, cells respond to mistargeted mitochondrial proteins by increasing activity of the proteasome in the cytosol (termed the “unfolded protein response activated by mistargeting of proteins” [UPRam] ). The presence and relevance of this response in higher eukaryotes is unclear. Here, we demonstrate that defects in mitochondrial protein import in Caenorhabditis elegans lead to proteasome activation and life span extension. Both proteasome activation and life span prolongation partially depend on ATFS-1, despite its lack of influence on proteasomal gene transcription. Importantly, life span prolongation depends on the fully assembled proteasome. Our data provide a link between mitochondrial dysfunction and proteasomal activity and demonstrate its direct relevance to mechanisms that promote longevity.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001302
DOI:
10.1371/journal.pbio.3001302.g001
DOI:
10.1371/journal.pbio.3001302.g002
DOI:
10.1371/journal.pbio.3001302.g003
DOI:
10.1371/journal.pbio.3001302.g004
DOI:
10.1371/journal.pbio.3001302.g005
DOI:
10.1371/journal.pbio.3001302.g006
DOI:
10.1371/journal.pbio.3001302.g007
DOI:
10.1371/journal.pbio.3001302.s001
DOI:
10.1371/journal.pbio.3001302.s002
DOI:
10.1371/journal.pbio.3001302.s003
DOI:
10.1371/journal.pbio.3001302.s004
DOI:
10.1371/journal.pbio.3001302.s005
DOI:
10.1371/journal.pbio.3001302.s006
DOI:
10.1371/journal.pbio.3001302.s007
DOI:
10.1371/journal.pbio.3001302.s008
DOI:
10.1371/journal.pbio.3001302.s009
DOI:
10.1371/journal.pbio.3001302.s010
DOI:
10.1371/journal.pbio.3001302.s011
DOI:
10.1371/journal.pbio.3001302.s012
DOI:
10.1371/journal.pbio.3001302.s013
DOI:
10.1371/journal.pbio.3001302.s014
DOI:
10.1371/journal.pbio.3001302.s015
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2126773-X
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