Armc12, an armadillo repeat-containing protein, is a mitochondrial peripheral membrane protein. It plays a crucial role in regulating mitochondrial dynamics, especially during spermiogenesis. It is involved in the formation of the mitochondrial sheath in sperm, which is essential for sperm motility, thus being of great importance for male fertility [1,2]. Genetic models like knockout mice are valuable tools for studying its functions.

In Armc12-null mice, abnormal mitochondrial coiling along the flagellum occurs due to improper elongation at the mitochondrial interlocking step during spermiogenesis. This leads to reduced sperm motility and male sterility. ARMC12 functions as an adherence factor between mitochondria in cultured cells. It interacts with mitochondrial proteins such as MIC60, VDAC2, VDAC3, as well as TBC1D21 and GK2 in testicular germ cells, with TBC1D21 being essential for the interaction between ARMC12 and VDAC proteins in vivo. These interactions are required for mitochondrial sheath formation [1]. In human studies, biallelic mutations in ARMC12 were identified in patients with asthenozoospermia, whose spermatozoa showed multiple midpiece defects similar to those in Armc12-knockout mice [2].

In conclusion, Armc12 is essential for regulating spatiotemporal mitochondrial dynamics to form the mitochondrial sheath during spermiogenesis. The study of Armc12-null mouse models has significantly contributed to understanding male infertility caused by asthenozoospermia and multiple midpiece defects in humans [1,2].

References:

1. Shimada, Keisuke, Park, Soojin, Miyata, Haruhiko, Matzuk, Martin M, Ikawa, Masahito. . ARMC12 regulates spatiotemporal mitochondrial dynamics during spermiogenesis and is required for male fertility. In Proceedings of the National Academy of Sciences of the United States of America, 118, . doi:10.1073/pnas.2018355118. https://pubmed.ncbi.nlm.nih.gov/33536340/

2. Liu, Wensheng, Wei, Xiaoli, Liu, Xiaoyan, Sha, Yanwei, Wang, Yifeng. 2022. Biallelic mutations in ARMC12 cause asthenozoospermia and multiple midpiece defects in humans and mice. In Journal of medical genetics, 60, 154-162. doi:10.1136/jmedgenet-2021-108137. https://pubmed.ncbi.nlm.nih.gov/35534203/