Aman, Yahyah;
Erinjeri, Annmary Paul;
Tataridas-Pallas, Nikolaos;
Williams, Rhianna;
Wellman, Rachel;
Chapman, Hannah;
Labbadia, John;
(2022)
Loss of MTCH-1 suppresses age-related proteostasis collapse through the inhibition of programmed cell death factors.
Cell Reports
, 41
(8)
, Article 111690. 10.1016/j.celrep.2022.111690.
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Abstract
The age-related loss of protein homeostasis (proteostasis) is at the heart of numerous neurodegenerative diseases. Therefore, finding ways to preserve proteome integrity in aged cells may be a powerful way to promote long-term health. Here, we show that reducing the activity of a highly conserved mitochondrial outer membrane protein, MTCH-1/MTCH2, suppresses age-related proteostasis collapse in Caenorhabditis elegans without disrupting development, growth, or reproduction. Loss of MTCH-1 does not influence proteostasis capacity in aged tissues through previously described pathways but instead operates by reducing CED-4 levels. This results in the sequestration of HSP-90 by inactive CED-3, which in turn leads to an increase in HSF-1 activity, transcriptional remodeling of the proteostasis network, and maintenance of proteostasis capacity with age. Together, our findings reveal a role for programmed cell death factors in determining proteome health and suggest that inhibiting MTCH-1 activity in adulthood may safeguard the aging proteome and suppress age-related diseases.
Type: | Article |
---|---|
Title: | Loss of MTCH-1 suppresses age-related proteostasis collapse through the inhibition of programmed cell death factors |
Location: | United States |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1016/j.celrep.2022.111690 |
Publisher version: | https://doi.org/10.1016/j.celrep.2022.111690 |
Language: | English |
Additional information: | Copyright © 2022 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | protein homeostasis, aging, HSF-1, molecular chaperones, MTCH-1, mitochondria, programmed cell death, Caenorhabditis elegans, HSP90 |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment |
URI: | https://discovery.ucl.ac.uk/id/eprint/10160791 |
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