Spata33, also known as 4732415M23Rik or C16orf55, is a gene conserved in mammalian species. It has a significant role in spermatogenesis and is predominantly expressed in the testes [5]. Functionally, it is involved in mitophagy, a process crucial for maintaining cellular homeostasis by selectively degrading damaged and superfluous mitochondria via the autophagy-lysosome pathway [1,2].

Gene-modified mouse models have provided key insights into Spata33's functions. Spata33 knockout mice exhibit reduced sperm motility due to an inflexible midpiece, leading to impaired male fertility, as sperm calcineurin fails to localize to the mitochondria in the knockout testis [4]. In addition, Spata33 knockout in TM4 cells affects cell migration, cell cycle progression, and the formation of F-actin and cell adhesion complexes [3]. In male germline cells, Spata33 knockout inhibits autophagy, while its overexpression promotes autophagosome formation for mitochondrial sequestration, indicating its role in conferring selectivity for mitochondrial degradation and promoting mitophagy [2].

In conclusion, Spata33 is essential for spermatogenesis, sperm motility, and mitophagy in male germline cells. The use of Spata33 knockout mouse models has revealed its role in specific biological processes related to male fertility and cellular homeostasis, highlighting its importance in understanding male infertility and related biological mechanisms [2,3,4].

References:

1. Xu, Xu, Zhang, Ying, Cheng, Hanhua, Zhou, Rongjia. 2021. SPATA33 functions as a mitophagy receptor in mammalian germline. In Autophagy, 17, 1284-1286. doi:10.1080/15548627.2021.1909836. https://pubmed.ncbi.nlm.nih.gov/33818286/

2. Zhang, Ying, Xu, Xu, Hu, Mengxin, Cheng, Hanhua, Zhou, Rongjia. 2020. SPATA33 is an autophagy mediator for cargo selectivity in germline mitophagy. In Cell death and differentiation, 28, 1076-1090. doi:10.1038/s41418-020-00638-2. https://pubmed.ncbi.nlm.nih.gov/33087875/

3. Zhang, Ying. 2022. SPATA33 affects the formation of cell adhesion complex by interacting with CTNNA3 in TM4 cells. In Cell and tissue research, 389, 145-157. doi:10.1007/s00441-022-03631-y. https://pubmed.ncbi.nlm.nih.gov/35536443/

4. Miyata, Haruhiko, Oura, Seiya, Morohoshi, Akane, Abbasi, Ferheen, Ikawa, Masahito. . SPATA33 localizes calcineurin to the mitochondria and regulates sperm motility in mice. In Proceedings of the National Academy of Sciences of the United States of America, 118, . doi:10.1073/pnas.2106673118. https://pubmed.ncbi.nlm.nih.gov/34446558/

5. Chen, Hengling, Yi, Minhan, Sheng, Yue, Cheng, Hanhua, Zhou, Rongjia. 2013. A novel testis-enriched gene Spata33 is expressed during spermatogenesis. In PloS one, 8, e67882. doi:10.1371/journal.pone.0067882. https://pubmed.ncbi.nlm.nih.gov/23844118/