Caenorhabditis elegans homolog of FAM210 is required for oogenesis and reproduction

Abstract 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 many tissues, including the intestine, muscle, hypodermis, and germline, and its encoded protein predominantly localizes to mitochondria. y56a3a.22 deletion mutants are sterile due 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 induced 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 Fam210 family.