Biology subjects

Shravage, B. V.

Publications and source records attributed to Shravage, B. V..

3 recordsLinked to original sources

bioRxiv2024

Autophagy is dispensable in germline stem cells but is required in the cap cells for their maintenance in the Drosophila ovarian niche

Autophagy is a cytoprotective mechanism responsible for the maintenance and long-term survival of various cell types, including stem cells. However, its role in the Germline stem cell (GSC)-niche, including its effects on GSCs and niche cells, remains unexplored. We demonstrate that autophagy flux in female Drosophila GSCs is low and dependent on the core autophagy gene, Atg5. However, the maintenance of Atg5-/- GSCs within the GSC-niche was unaffected. In contrast, disruption of autophagy within the cap cells (niche cells) leads to the loss of both cap cells and GSCs during aging. Further, reduced autophagy in cap cells severely impairs the crucial GSC self-renewal signal mediated by BMP-pMad emanating from the cap cells post-midlife. Autophagy was essential for the long-term survival of cap cells. Our study reveals a differential role for autophagy, which is dispensable in GSCs but necessary in niche cells, where it supports signaling and survival to maintain GSCs.

developmental biology↗

bioRxiv2022

Atg1 and Marf collaborate to maintain germline stem cells in Drosophila

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

cell biology↗

bioRxiv2022

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

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

developmental biology↗