Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell. 2024 Aug 22;187(17):4605-4620.e17. doi: 10.1016/j.cell.2024.06.010. Epub 2024 Jul 2.
The ability of mitochondria to coordinate stress responses across tissues is critical for health. In C. elegans, neurons experiencing mitochondrial stress elicit an inter-tissue signaling pathway through the release of mitokine signals, such as serotonin or the Wnt ligand EGL-20, which activate the mitochondrial unfolded protein response (UPR) in the periphery to promote organismal health and lifespan. We find that germline mitochondria play a surprising role in neuron-to-periphery UPR signaling. Specifically, we find that germline mitochondria signal downstream of neuronal mitokines, Wnt and serotonin, and upstream of lipid metabolic pathways in the periphery to regulate UPR activation. We also find that the germline tissue itself is essential for UPR signaling. We propose that the germline has a central signaling role in coordinating mitochondrial stress responses across tissues, and germline mitochondria play a defining role in this coordination because of their inherent roles in germline integrity and inter-tissue signaling.
线粒体协调组织间应激反应的能力对健康至关重要。在秀丽隐杆线虫中，经历线粒体应激的神经元通过释放细胞因子信号，如血清素或 Wnt 配体 EGL-20，引发组织间信号通路，激活外周细胞的未折叠蛋白反应 (UPR)，从而促进机体健康和寿命。我们发现生殖系线粒体在神经元到外周 UPR 信号转导中起着惊人的作用。具体来说，我们发现生殖系线粒体信号转导位于神经元细胞因子、Wnt 和血清素的下游，以及位于外周脂代谢途径的上游，从而调节 UPR 的激活。我们还发现生殖系组织本身对于 UPR 信号转导是必需的。我们提出，生殖系在协调组织间线粒体应激反应中具有核心信号作用，而生殖系线粒体在这种协调中起着决定性作用，因为它们在生殖系完整性和组织间信号转导中具有固有作用。
