Kastor and Polluks polypeptides encoded by a single gene locus cooperatively regulate VDAC and spermatogenesis

Shintaro Mise, Akinobu Matsumoto (), Keisuke Shimada, Toshiaki Hosaka, Masatomo Takahashi, Kazuya Ichihara, Hideyuki Shimizu, Chisa Shiraishi, Daisuke Saito, Mikita Suyama, Tomoharu Yasuda, Toru Ide, Yoshihiro Izumi, Takeshi Bamba, Tomomi Kimura-Someya, Mikako Shirouzu, Haruhiko Miyata, Masahito Ikawa and Keiichi I. Nakayama ()
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Shintaro Mise: Kyushu University, Fukuoka
Akinobu Matsumoto: Kyushu University, Fukuoka
Keisuke Shimada: Osaka University
Toshiaki Hosaka: RIKEN Center for Biosystems Dynamics Research
Masatomo Takahashi: Kyushu University, Fukuoka
Kazuya Ichihara: Kyushu University, Fukuoka
Hideyuki Shimizu: Kyushu University, Fukuoka
Chisa Shiraishi: Kyushu University, Fukuoka
Daisuke Saito: Kyushu University, Fukuoka
Mikita Suyama: Kyushu University, Fukuoka
Tomoharu Yasuda: Hiroshima University, Hiroshima
Toru Ide: Okayama University, Okayama
Yoshihiro Izumi: Kyushu University, Fukuoka
Takeshi Bamba: Kyushu University, Fukuoka
Tomomi Kimura-Someya: RIKEN Center for Biosystems Dynamics Research
Mikako Shirouzu: RIKEN Center for Biosystems Dynamics Research
Haruhiko Miyata: Osaka University
Masahito Ikawa: Osaka University
Keiichi I. Nakayama: Kyushu University, Fukuoka

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-28677-y

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