TY - JOUR
T1 - Oocyte mitophagy is critical for extended reproductive longevity
AU - Cota, Vanessa
AU - Sohrabi, Salman
AU - Kaletsky, Rachel
AU - Murphy, Coleen T.
N1 - Funding Information:
This project was funded in part by the Global Consortium for Reproductive Longevity and Equality through the Buck Institute, GCRLE-0220, to CTM. NIGMS Training grant, T32GM007388, Princeton University Molecular Biology Department. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
Copyright © 2022 Cota et al.
PY - 2022/9/20
Y1 - 2022/9/20
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pgen.1010400
DO - 10.1371/journal.pgen.1010400
M3 - Article
C2 - 36126046
AN - SCOPUS:85139536075
VL - 18
JO - PLoS Genetics
JF - PLoS Genetics
SN - 1553-7390
IS - 9
M1 - e1010400
ER -