Oocyte mitophagy is critical for extended reproductive longevity.

TitleOocyte mitophagy is critical for extended reproductive longevity.
Publication TypeJournal Article
Year of Publication2022
AuthorsCota, V, Sohrabi, S, Kaletsky, R, Murphy, CT
JournalPLoS Genet
Volume18
Issue9
Paginatione1010400
Date Published2022 Sep
ISSN1553-7404
KeywordsAdult, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Female, Humans, Insulins, Longevity, Mitophagy, Oocytes, Reproduction
Abstract

<p>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.</p>

DOI10.1371/journal.pgen.1010400
Alternate JournalPLoS Genet
PubMed ID36126046
PubMed Central IDPMC9524673
Grant ListT32 GM007388 / GM / NIGMS NIH HHS / United States