# Programmed mitophagy at the oocyte-to-zygote transition promotes species immortality

## TL;DR

This study reveals a programmed mitophagy process during the oocyte-to-zygote transition that helps preserve mitochondrial health and supports species survival.

## Contribution

The discovery of mitophagy at the oocyte-to-zygote transition (MOZT) as a novel mechanism for eliminating damaged mtDNA.

## Key findings

- MOZT requires mitochondrial fragmentation and the FUNDC1 receptor, but not PINK1 or BNIP3.
- Impaired MOZT increases inherited mtDNA damage and reduces embryonic survival.
- Accumulated mtDNA damage across generations leads to population extinction.

## Abstract

The quality of mitochondria inherited from the oocyte determines embryonic viability, metabolic health throughout progeny lifetime, and future generation endurance. High levels of endogenous reactive oxygen species and exogenous toxicants are threats to mitochondrial DNA (mtDNA) in fully developed oocytes. Deleterious mtDNA is commonly detected in developed oocytes, but is absent in embryos, suggesting the existence of a cryptic purifying selection mechanism. Here we discover that in C. elegans, the onset of oocyte-to-zygote transition (OZT) developmentally triggers a rapid mitophagy event. We show that mitophagy at OZT (MOZT) requires mitochondrial fragmentation, the macroautophagy pathway, and the mitophagy receptor FUNDC1, but not the prevalent mitophagy factors PINK1 and BNIP3. Impaired MOZT leads to increased deleterious mtDNA inheritance and decreases embryonic survival. Inherited mtDNA damage accumulates across generations, leading to the extinction of descendent populations. Thus, MOZT represents a strategy that preserves mitochondrial health during the mother-to-offspring transmission and promotes species continuity.