Mitochondrial DNA quality control in the female germline requires a unique programmed mitophagy

Mitochondria have their own DNA (mtDNA), which is susceptible to the accumulation of disease-causing mutations. To prevent deleterious mutations from being inherited, the female germline has evolved a conserved quality control mechanism that remains poorly understood. Here, through a large-scale screen, we uncover a unique programmed germline mitophagy (PGM) that is essential for mtDNA quality control. We find that PGM is developmentally triggered as germ cells enter meiosis by inhibition of the target of rapamycin complex 1 (TORC1). We identify a role for the RNA-binding protein Ataxin-2 (Atx2) in coordinating the timing of PGM with meiosis. We show that PGM requires the mitophagy receptor BNIP3, mitochondrial fission and translation factors, and members of the Atg1 complex, but not the mitophagy factors PINK1 and Parkin. Additionally, we report several factors that are critical for germline mtDNA quality control and show that pharmacological manipulation of one of these factors promotes mtDNA quality control. [Display omitted] •A screen uncovers numerous genes required for germline mtDNA quality control•A developmentally induced mitophagy plays a key role in mtDNA quality control•This mitophagy involves BNIP3, mitochondrial fission factors, and Atg1 complex•Atx2 regulates TORC1 to induce mitophagy, coupling mtDNA quality control to meiosis Palozzi et al. uncovered a unique programmed germline mitophagy (PGM) required to prevent the transmission of mutant mitochondrial DNA in the female Drosophila germline. PGM requires both canonical and non-canonical mitophagy factors and is developmentally coupled to the onset of meiosis by the regulation of TORC1.