DRP1-dependent mitochondrial fission initiates follicle cell differentiation during Drosophila oogenesis

Abstract

Reduced Drp1-mediated mitochondrial fission decreases cell cycle exit and prevents Notch-dependent follicle cell differentiation during oogenesis.

A novel mitochondrial pool of Cyclin E, regulated by Drp1, is linked to cell density dependent cell proliferation

“…After stage 6, the follicle cells exit the mitotic cycle to terminally differentiate into the epithelial cell layer, which is further patterned into various cell types (Klusza and Deng, 2011). We have previously reported differential mitochondrial regulation in the mitotic follicle cells and the differentiated-patterned main body follicle cells (MBCs) and posterior follicle cells (PFCs) (Mitra et al, 2012). Here, we found that the mtDmCycE pool was significantly higher in the MBCs than the PFCs or the mitotic follicle cells ( Fig.…”

“…We next sought to detect the new mtCycE pool in vivo in the Drosophila follicle cell layer where we have previously demonstrated specific mitochondrial regulation of CycE (Mitra et al, 2012). The follicle cell layer is the epithelial cell layer encapsulating the Drosophila egg chambers.…”

“…The emerging model suggests that cell cycle regulators regulate Drp1 (Taguchi et al, 2007;Kashatus et al, 2011;Horn et al, 2011), which, in turn, further regulates CycE levels in proliferating cells (Mitra, 2013). We have previously shown that although loss of Drp1 deregulates CycE in various cell contexts, it promotes aberrant cell proliferation only in the presence of EGFR signaling (Mitra et al, 2012). Using mammalian cells and Drosophila model systems in parallel, we report that a new mitochondrial pool of CycE, which can be modulated by Drp1, likely through regulation of mitochondrial energetics, is linked to control of cell proliferation in a cell-density-dependent manner.…”

“…Mitochondrial ATP-synthesizing capability can be directly or indirectly influenced by a certain group of proteins that directly modulate the ability of mitochondria to undergo fusion or fission events with each other (Westermann, 2010;Galloway et al, 2012). Reduction of the levels or activity of the key mitochondrial fission protein, dynamin-related protein 1 (Drp1, SwissProt O00429 in humans) leads to elevation of CycE levels in various mammalian cells and in Drosophila (Mitra et al, 2012(Mitra et al, , 2009Qian et al, 2012). The emerging model suggests that cell cycle regulators regulate Drp1 (Taguchi et al, 2007;Kashatus et al, 2011;Horn et al, 2011), which, in turn, further regulates CycE levels in proliferating cells (Mitra, 2013).…”

Giving microbes their due – animal life in a microbially dominant world

“…In addition to its well-recognized role as the 'powerhouse' of the cell, recent studies have indicated that the mitochondria control many more cellular functions (Mitra and Lippincott-Schwartz, 2010;Antico Arciuch et al, 2012;Friedman and Nunnari, 2014). For example, the mitochondrial network in the cell appears to be electrically coupled (De Giorgi et al, 2000) and coordinates such critical processes as cell death, cell proliferation, autophagy (Rambold and Lippincott-Schwartz, 2011), cell differentiation (Mitra et al, 2012) and aging (Lee and Wei, 2012). The view seems to be emerging that perhaps the mitochondrial network is actually the 'brains' of the cell, controlling much of the cell's processes, including activities of the nucleus.…”