Caenorhabditis elegans homologue of Fam210 is required for oogenesis and reproduction
Caenorhabditis elegans homologue of Fam210 is required for oogenesis and reproduction
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秀丽隐杆线虫 FAM210 同源物是卵子发生和繁殖所必需的
DOI：
10.1016/j.jgg.2020.10.008
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发表时间：
2020-11-20
影响因子：
5.9
通讯作者：
Chen, Caiyong
中科院分区：
文献类型：
--
作者：
Kang, Jing;Zhou, Hengda;Chen, Caiyong
线粒体是许多代谢过程的中心枢纽，包括柠檬酸循环、氧化磷酸化和脂肪酸氧化。最近的研究已经确定了一个新的线粒体蛋白家族Fam 210，它调节脊椎动物的骨代谢和红细胞发育。模式生物秀丽隐杆线虫有一个Fam 210基因，y56a3a.22，但它缺乏骨骼和红细胞。在这项研究中，我们报告Y56A3A.22在调节线粒体蛋白质稳态和生殖中起着至关重要的作用。线虫y56a3a.22在各种组织中表达，包括肠、肌肉、皮下组织和生殖系，并且其编码的蛋白质主要位于线粒体中。Y56a3a.22缺失突变体由于卵子发生受损而不育。Y56A3A.22的缺失诱导了线粒体未折叠蛋白反应（UPRmt），其通过ATFS-1依赖性途径介导，在组织如肠、生殖系、皮下组织和外阴肌肉中。我们进一步表明，不育和UPRmt诱导的Y56A3A.22缺乏症是不是由于系统性缺铁。总之，我们的研究揭示了Y56A3A.22在调节线粒体蛋白质稳态和卵子发生中的重要作用，并为探索线粒体代谢和生殖的调节机制以及Fam 210家族的基本作用提供了新的遗传工具。中国科学院遗传与发育生物学研究所版权所有（C）2020由Elsevier Limited和Science Press出版。All rights reserved.
Mitochondria are the central hub for many metabolic processes, including the citric acid cycle, oxidative phosphorylation, and fatty acid oxidation. Recent studies have identified a new mitochondrial protein family, Fam210, that regulates bone metabolism and red cell development in vertebrates. The model organism Caenorhabditis elegans has a Fam210 gene, y56a3a.22, but it lacks both bones and red blood cells. In this study, we report that Y56A3A.22 plays a crucial role in regulating mitochondrial protein homeostasis and reproduction. The nematode y56a3a.22 is expressed in various tissues, including the intestine, muscle, hypodermis, and germline, and its encoded protein is predominantly localized in mitochondria. y56a3a.22 deletion mutants are sterile owing to impaired oogenesis. Loss of Y56A3A.22 induced mitochondrial unfolded protein response (UPRmt), which is mediated through the ATFS-1-dependent pathway, in tissues such as the intestine, germline, hypodermis, and vulval muscle. We further show that infertility and UPRmt induces by Y56A3A.22 deficiency are not attributed to systemic iron deficiency. Together, our study reveals an important role of Y56A3A.22 in regulating mitochondrial protein homeostasis and oogenesis and provides a new genetic tool for exploring the mechanisms regulating mitochondrial metabolism and reproduction as well as the fundamental role of the Fam210 family. Copyright (C) 2020, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved.