Oral Presentation (Best Presentation Award)

Sperm...have...a...characteristic...structure...called...the...“mitochondrial...sheath,”... in...which...mitochondria...are... tightly... coiled...around...the...flagellum....However,... the...molecular...mechanisms... involved... in...the... formation...of... this...structure... have...not...been...well... studied.... In... this... study,...we... investigated... the... function...of...ARMC12... that... is... specifically... expressed... in... the...testis... to...clarify... the...molecular...mechanisms... involved... in... the... formation...of... the...mitochondrial... sheath.... We...generated...several... testis-enriched...gene...KO...mice...using... the...CRISPR/Cas9...system...and...examined... their... fertility...and...sperm...morphology....Armc12...KO...male...mice...are...infertile,...and...KO...spermatozoa...showed...abnormal... morphology...and...reduced...motility....Scanning...electron...microscopy...revealed...that...sperm...mitochondria...in...KO...mice... failed... to...elongate...properly...around... the... flagellum....ARMC12... is... localized...on... the...outer...membrane...of... sperm... mitochondria...as...a...peripheral...membrane...protein.... Immunoprecipitation...revealed...that...ARMC12... interacts...with... several... proteins,... including...VDAC2... and...VDAC3,...which... are... channel... proteins... localized... on... the... outer... mitochondrial...membrane,...and...TBC1D21,...which...is...expressed...specifically...in...the...testis. Tbc1d21...KO...mice...showed...the...same...abnormalities...in...mitochondrial...sheath...formation...as...Armc12...KO...mice,...and... the...protein... interaction...between...ARMC12...and...VDAC...was...not...observed... in...Tbc1d21...KO...testis.... In...addition,... experiments...using...cultured...cells...showed...that...mitochondria... in...ARMC12-expressing...cells...aggregate,... indicating... that...ARMC12...acts...as...an...adherence...factor...between...mitochondria. These...results...suggest...that...ARMC12...acts...as...an...adherence...factor...between...mitochondria...by...cooperating...with... TBC1D21,...and...uses...VDAC...proteins...as...a...scaffold....This...suggests...that...ARMC12...enables...sperm...mitochondria...to... correctly...elongate...around...the...flagellum...during...spermatogenesis,...resulting...in...the...formation...of...a...finely...organized... mitochondrial...sheath. ARMC12 enables mitochondrial sheath formation in cooperation with TBC1D21