Fission and PINK-1-mediated mitophagy are required for Insulin/IGF-1 signaling mutant reproductive longevity

Cota, Vanessa; Murphy, Coleen T.

Women’s reproductive cessation is the earliest sign of human aging and is caused by decreasing oocyte quality. Similarly, C. elegans’ reproduction declines with age and is caused by oocyte quality decline. Aberrant mitochondrial dynamics are a hallmark of age-related dysfunction, but the role of mitochondrial morphology in reproductive aging is largely unknown. 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. By contrast, daf-2 mutants require fission, but not fusion, for reproductive span extension. daf-2 mutant oocytes’ mitochondria are punctate (fissioned) and may be primed for mitophagy, as loss of the mitophagy regulator PINK-1 shortens daf-2’s reproductive span. Our data suggest that daf-2 maintain oocyte mitochondria quality with age via a shift toward punctate mitochondrial morphology and mitophagy to extend reproductive longevity.