Atg1 modulates mitochondrial dynamics to promote germline stem cell maintenance in Drosophila.

Abstract

Mitochondrial dynamics (fusion and fission) are necessary for stem cell maintenance and differentiation. However, the relationship 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. Disrupting Atg1 function led to mitochondrial fusion in developing cysts. The fusion was a result of an increase in Marf levels in both GSCs and cysts, and the fusion phenotype could be rescued by overexpression of Drp1 or by depleting Marf via RNAi in Atg1-depleted cyst cells. Interestingly, double knockdown of both Atg1:Marf affected ovariole size and the number of vitellogenic oocytes. While Atg1:Marf knockdown led to decrease in germ cell number. Strikingly, Atg1:Marf double knockdown leads to a dramatic loss of GSCs, GCs and a total loss of vitellogenic stages, suggesting a block in oogenesis. Overall, our results demonstrate that Drp1, Marf and Atg1 function together to influence female GSC maintenance and their differentiation into cysts. Research HighlightsO_LIAtg1, in addition to its role in mitophagy, influences mitochondrial dynamics during oogenesis through modulation of Marf. C_LIO_LIAtg1 and Marf promote Germline stem cell maintenance in Drosophila. C_LI