Institute for Genetics, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Greece; Division of Basic Sciences, School of Medicine, University of Crete, Heraklion, Greece.
Cell Rep. 2024 Jun 25;43(6):114336. doi: 10.1016/j.celrep.2024.114336. Epub 2024 Jun 7.
Proteome integrity is fundamental for cellular and organismal homeostasis. The mitochondrial unfolded protein response (UPR), a key component of the proteostasis network, is activated in a non-cell-autonomous manner in response to mitochondrial stress in distal tissues. However, the importance of inter-tissue communication for UPR inducibility under physiological conditions remains elusive. Here, we show that an intact germline is essential for robust UPR induction in the Caenorhabditis elegans somatic tissues. A series of nematode mutants with germline defects are unable to respond to genetic or chemical UPR inducers. Our genetic analysis suggests that reproductive signals, rather than germline stem cells, are responsible for somatic UPR induction. Consistent with this observation, we show that UPR is sexually dimorphic, as male nematodes are inherently unresponsive to mitochondrial stress. Our findings highlight a paradigm of germline-somatic communication and suggest that reproductive cessation is a primary cause of age-related UPR decline.
蛋白质组完整性是细胞和机体稳态的基础。线粒体未折叠蛋白反应 (UPR) 是蛋白质稳态网络的关键组成部分，它以非细胞自主的方式响应远端组织中的线粒体应激而被激活。然而，在生理条件下，组织间通讯对于 UPR 的诱导能力的重要性仍不清楚。在这里，我们表明完整的生殖系对于秀丽隐杆线虫体组织中强大的 UPR 诱导是必不可少的。一系列具有生殖系缺陷的线虫突变体无法对遗传或化学 UPR 诱导剂产生反应。我们的遗传分析表明，生殖信号而不是生殖干细胞负责体 UPR 的诱导。与这一观察结果一致，我们表明 UPR 存在性别二态性，因为雄性线虫对线粒体应激固有地无反应。我们的研究结果突出了生殖系与体组织通讯的范例，并表明生殖停止是与年龄相关的 UPR 下降的主要原因。
