Autophagy slows the aging of Germline stem cells in Drosophila through modulation of E-cadherin

Abstract

Autophagy is a conserved process that degrades cytoplasmic components and organelles in metazoan cells including germline stem cells. Although autophagy is implicated in the aging of stem cells, the precise mechanism are still unknown. Here we show that elevating autophagy by overexpressing (OE) Drosophila Autophagy-related gene 8a (Atg8a) in the female Germline stem cells (GSCs) delays their loss due to aging. However, sustained elevated autophagy levels in old flies promote GSC loss due to cell death. In contrast, knockdown of Atg8a (Atg8aRNAi) in GSCs accelerates their loss. Atg8aOE GSCs show elevated autophagy flux, and increased mitotic activity even at 8 weeks of age. Atg8aOE GSCs possess smaller-sized mitochondria and exhibit reduced mitochondrial oxidative stress in the GSCs. However, in contrast Atg8aRNAi GSCs have elevated mitochondrial ROS and possess larger mitochondria. Finally, our data show that Atg8aOE GSCs occupy the stem cell niche for longer duration with the aid of elevated E-cadherin at the GSC-cap cell contact sites. Our data suggests that elevated autophagy promotes GSC maintenance and activity, and delays their aging. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=142 SRC="FIGDIR/small/486570v2_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@1210949org.highwire.dtl.DTLVardef@1e8a9a3org.highwire.dtl.DTLVardef@1d9344aorg.highwire.dtl.DTLVardef@f81a83_HPS_FORMAT_FIGEXP M_FIG C_FIG