TY - JOUR
T1 - Kastor and Polluks polypeptides encoded by a single gene locus cooperatively regulate VDAC and spermatogenesis
AU - Mise, Shintaro
AU - Matsumoto, Akinobu
AU - Shimada, Keisuke
AU - Hosaka, Toshiaki
AU - Takahashi, Masatomo
AU - Ichihara, Kazuya
AU - Shimizu, Hideyuki
AU - Shiraishi, Chisa
AU - Saito, Daisuke
AU - Suyama, Mikita
AU - Yasuda, Tomoharu
AU - Ide, Toru
AU - Izumi, Yoshihiro
AU - Bamba, Takeshi
AU - Kimura-Someya, Tomomi
AU - Shirouzu, Mikako
AU - Miyata, Haruhiko
AU - Ikawa, Masahito
AU - Nakayama, Keiichi I.
N1 - Funding Information:
We thank L. Cui, K. Ito, Y. Ishizuka-Katsura, and the Research Promotion Unit of the Medical Institute of Bioregulation at Kyushu University for technical assistance, as well as A. Ohta for help with preparation of the manuscript. We also thank Y. Ohkawa for the help in generating the monoclonal antibodies. This research was supported in part by grant JP21am0101082 from the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research [BINDS]) of the Japan Agency for Medical Research and Development (AMED), as well as by KAKENHI grants from Japan Society for the Promotion of Science (JSPS) and the Ministry of Education, Culture, Sports, Science, and Technology of Japan to K.S. (JP20K16107), A.M. (JP20H05928 and JP20K21397), and K.I.N. (JP18H05215).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Although several long noncoding RNAs (lncRNAs) have recently been shown to encode small polypeptides, those in testis remain largely uncharacterized. Here we identify two sperm-specific polypeptides, Kastor and Polluks, encoded by a single mouse locus (Gm9999) previously annotated as encoding a lncRNA. Both Kastor and Polluks are inserted in the outer mitochondrial membrane and directly interact with voltage-dependent anion channel (VDAC), despite their different amino acid sequences. Male VDAC3-deficient mice are infertile as a result of reduced sperm motility due to an abnormal mitochondrial sheath in spermatozoa, and deficiency of both Kastor and Polluks also severely impaired male fertility in association with formation of a similarly abnormal mitochondrial sheath. Spermatozoa lacking either Kastor or Polluks partially recapitulate the phenotype of those lacking both. Cooperative function of Kastor and Polluks in regulation of VDAC3 may thus be essential for mitochondrial sheath formation in spermatozoa and for male fertility.
AB - Although several long noncoding RNAs (lncRNAs) have recently been shown to encode small polypeptides, those in testis remain largely uncharacterized. Here we identify two sperm-specific polypeptides, Kastor and Polluks, encoded by a single mouse locus (Gm9999) previously annotated as encoding a lncRNA. Both Kastor and Polluks are inserted in the outer mitochondrial membrane and directly interact with voltage-dependent anion channel (VDAC), despite their different amino acid sequences. Male VDAC3-deficient mice are infertile as a result of reduced sperm motility due to an abnormal mitochondrial sheath in spermatozoa, and deficiency of both Kastor and Polluks also severely impaired male fertility in association with formation of a similarly abnormal mitochondrial sheath. Spermatozoa lacking either Kastor or Polluks partially recapitulate the phenotype of those lacking both. Cooperative function of Kastor and Polluks in regulation of VDAC3 may thus be essential for mitochondrial sheath formation in spermatozoa and for male fertility.
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U2 - 10.1038/s41467-022-28677-y
DO - 10.1038/s41467-022-28677-y
M3 - Article
C2 - 35228556
AN - SCOPUS:85125570733
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1071
ER -