National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Dev Cell. 2023 Nov 6;58(21):2249-2260.e9. doi: 10.1016/j.devcel.2023.08.007. Epub 2023 Aug 29.
In multicellular lives, the differentiation of stem cells and progenitor cells is often accompanied by a transition from glycolysis to mitochondrial oxidative phosphorylation (OXPHOS). However, the underlying mechanism of this metabolic transition remains largely unknown. In this study, we investigate the role of mechanical stress in activating OXPHOS during differentiation of the female germline cyst in Drosophila. We demonstrate that the surrounding somatic cells flatten the 16-cell differentiating cyst, resulting in an increase of the membrane tension of germ cells inside the cyst. This mechanical stress is necessary to maintain cytosolic Ca concentration in germ cells through a mechanically activated channel, transmembrane channel-like. The sustained cytosolic Ca triggers a CaMKI-Fray-JNK signaling relay, leading to the transcriptional activation of OXPHOS in differentiating cysts. Our findings demonstrate a molecular link between cell mechanics and mitochondrial energy metabolism, with implications for other developmentally orchestrated metabolic transitions in mammals.
在多细胞生物中，干细胞和祖细胞的分化通常伴随着从糖酵解到线粒体氧化磷酸化（OXPHOS）的转变。然而，这种代谢转变的潜在机制在很大程度上仍然未知。在这项研究中，我们研究了机械应力在果蝇雌性生殖细胞囊的分化过程中激活 OXPHOS 的作用。我们证明，周围的体细胞使 16 细胞分化的囊扁平化，导致囊内生殖细胞的膜张力增加。这种机械应力通过机械激活通道，跨膜通道样，对于维持生殖细胞质内的 Ca 浓度是必要的。持续的细胞质 Ca 触发 CaMKI-Fray-JNK 信号传递，导致分化囊中的 OXPHOS 的转录激活。我们的发现表明细胞力学和线粒体能量代谢之间存在分子联系，这对哺乳动物中其他发育协调的代谢转变具有重要意义。
