Reference - Detail
| RRC ID | 76112 |
|---|---|
| Author | Aman Y, Erinjeri AP, Tataridas-Pallas N, Williams R, Wellman R, Chapman H, Labbadia J. |
| Title | Loss of MTCH-1 suppresses age-related proteostasis collapse through the inhibition of programmed cell death factors. |
| Journal | Cell Rep |
| 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. |
| Volume | 41(8) |
| Pages | 111690 |
| Published | 2022-11-22 |
| DOI | 10.1016/j.celrep.2022.111690 |
| PII | S2211-1247(22)01564-9 |
| PMID | 36417880 |
| MeSH | Animals Apoptosis Caenorhabditis elegans / metabolism Protein Folding Proteome* / metabolism Proteostasis* / physiology |
| Altmetric score |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 21 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm1108 |