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Oocyte mitophagy is critical for extended reproductive longevity

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 ro...

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Autores principales: Cota, Vanessa, Sohrabi, Salman, Kaletsky, Rachel, Murphy, Coleen T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9524673/
https://www.ncbi.nlm.nih.gov/pubmed/36126046
http://dx.doi.org/10.1371/journal.pgen.1010400
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author Cota, Vanessa
Sohrabi, Salman
Kaletsky, Rachel
Murphy, Coleen T.
author_facet Cota, Vanessa
Sohrabi, Salman
Kaletsky, Rachel
Murphy, Coleen T.
author_sort Cota, Vanessa
collection PubMed
description 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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spelling pubmed-95246732022-10-01 Oocyte mitophagy is critical for extended reproductive longevity Cota, Vanessa Sohrabi, Salman Kaletsky, Rachel Murphy, Coleen T. PLoS Genet Research Article 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. Public Library of Science 2022-09-20 /pmc/articles/PMC9524673/ /pubmed/36126046 http://dx.doi.org/10.1371/journal.pgen.1010400 Text en © 2022 Cota et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Cota, Vanessa
Sohrabi, Salman
Kaletsky, Rachel
Murphy, Coleen T.
Oocyte mitophagy is critical for extended reproductive longevity
title Oocyte mitophagy is critical for extended reproductive longevity
title_full Oocyte mitophagy is critical for extended reproductive longevity
title_fullStr Oocyte mitophagy is critical for extended reproductive longevity
title_full_unstemmed Oocyte mitophagy is critical for extended reproductive longevity
title_short Oocyte mitophagy is critical for extended reproductive longevity
title_sort oocyte mitophagy is critical for extended reproductive longevity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9524673/
https://www.ncbi.nlm.nih.gov/pubmed/36126046
http://dx.doi.org/10.1371/journal.pgen.1010400
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