Reference - Detail
| RRC ID | 76148 |
|---|---|
| Author | Cota V, Sohrabi S, Kaletsky R, Murphy CT. |
| Title | Oocyte mitophagy is critical for extended reproductive longevity. |
| Journal | PLoS Genet |
| Abstract |
Women's reproductive cessation is the earliest sign of human aging and is caused by decreasing oocyte quality. Similarly, C. elegans' reproduction declines in mid-adulthood and is caused by oocyte quality decline. Aberrant mitochondrial morphology is a hallmark of age-related dysfunction, but the role of mitochondrial morphology and dynamics in reproductive aging is unclear. We examined the requirements for mitochondrial fusion and fission in oocytes of both wild-type worms and the long-lived, long-reproducing insulin-like receptor mutant daf-2. We find that normal reproduction requires both fusion and fission, but that daf-2 mutants utilize a shift towards fission, but not fusion, to extend their reproductive span and oocyte health. daf-2 mutant oocytes' mitochondria are punctate (fissioned) and this morphology is primed for mitophagy, as loss of the mitophagy regulator PINK-1 shortens daf-2's reproductive span. daf-2 mutants maintain oocyte mitochondria quality with age at least in part through a shift toward punctate mitochondrial morphology and subsequent mitophagy. Supporting this model, Urolithin A, a metabolite that promotes mitophagy, extends reproductive span in wild-type mothers-even in mid-reproduction-by maintaining youthful oocytes with age. Our data suggest that promotion of mitophagy may be an effective strategy to maintain oocyte health with age. |
| Volume | 18(9) |
| Pages | e1010400 |
| Published | 2022-9-1 |
| DOI | 10.1371/journal.pgen.1010400 |
| PII | PGENETICS-D-22-00628 |
| PMID | 36126046 |
| PMC | PMC9524673 |
| MeSH | Adult Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Female Humans Insulins* Longevity / genetics Mitophagy / genetics Oocytes / metabolism Reproduction / genetics |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 9 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm1108 tm1133 tm1779 |