Atg1 modulates mitochondrial dynamics to promote germline stem cell maintenance inDrosophila

Abstract

Mitochondrial dynamics (fusion and fission) has been demonstrated to necessary for stem cell maintenance and differentiation, however, the relation between mitophagy, mitochondrial dynamics and stem cell exhaustion is not clearly understood. Here we report the multifaceted role of Atg1 in mitophagy, mitochondrial dynamics and stem cell maintenance in female germline stem cells (GSCs) in Drosophila. We found that depletion of Atg1 in GSCs leads to impaired autophagy (mitophagy) as measured by reduced formation of autophagosomes, increased accumulation of p62/Ref(2)P and accumulation of damaged mitochondria. We observed increased generation of mitochondrial reactive oxygen species (mROS) in GSCs with depleted Atg1 and mitochondrial clustering/fusion in cysts with Atg1 knockdown (Atg1KD). The mitochondrial clustering/fusion observed in Atg1KD cysts was due to increase in Marf levels and the mitochondrial phenotype could be rescued by overexpression of Drp1 or by depleting Marf via RNAi in Atg1KD cyst cells. Interestingly, double knockdown of both Atg1:Drp1and Atg1:Marf affected ovariole size, number of GCs and the number of vitellogenic oocytes. Strikingly, Atg1:Marf double knockdown leads to loss of GSCs, differentiated GCs and a total loss of vitellogenic stages suggesting block in oogenesis. Overall, our results demonstrate that Drp1, Marf and Atg1 function together to influence female germline stem cell maintenance and differentiation of cystoblasts into cysts.