Abstract：
Proteome integrity is fundamental for cellular and organismal homeostasis. The mitochondrial unfolded protein response (UPRmt), 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 UPRmt inducibility under physiological conditions remains elusive. Here, we show that an intact germline is essential for robust UPRmt induction in the Caenorhabditis elegans somatic tissues. A series of nematode mutants with germline defects are unable to respond to genetic or chemical UPRmt inducers. Our genetic analysis suggests that reproductive signals, rather than germline stem cells, are responsible for somatic UPRmt induction. Consistent with this observation, we show that UPRmt 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 UPRmt decline.
摘要：
蛋白质组完整性是细胞和生物体稳态的基础。线粒体未折叠蛋白反应（UPRmt），蛋白质稳定网络的关键组成部分，响应于远端组织中的线粒体应激而以非细胞自主方式被激活。然而,在生理条件下，组织间通讯对UPRmt诱导性的重要性仍然难以捉摸。这里,我们表明，完整的种系对于秀丽隐杆线虫体细胞组织中强大的UPRmt诱导至关重要。一系列具有种系缺陷的线虫突变体无法对遗传或化学UPRmt诱导物作出反应。我们的遗传分析表明生殖信号，而不是生殖干细胞，负责体细胞UPRmt诱导。与这一观察一致，我们证明UPRmt是性二态的，因为雄性线虫本质上对线粒体应激无反应。我们的发现强调了种系-体细胞交流的范例，并表明生殖停止是与年龄相关的UPRmt下降的主要原因。
