Caseinolytic mitochondrial matrix peptidase X is essential for homologous chromosome synapsis and recombination during meiosis of male mouse germ cells  

作　　者：Hai-Wei Feng Yu Zhao Yan-Ling Gao Dong-Teng Liu Li-Jun Huo 

机构地区：[1]Key Laboratory of Agricultural Animal Genetics,Breeding and Reproduction,Education Ministry of China,College of Animal Science and Technology,Huazhong Agricultural University,Wuhan 430070,China [2]Shenzhen Key Laboratory of Fertility Regulation,Reproductive Medicine Center,The University of Hong Kong-Shenzhen Hospital,Shenzhen 518053,China [3]Maternal-Fetal Medicine Institute,Department of Obstetrics and Gynaecology,Shenzhen Baoan Women's and Children's Hospital,Jinan University,Shenzhen 518100,China [4]Department of Obstetrics and Gynaecology,Li Ka Shing Faculty of Medicine,The University of Hong Kong,Hong Kong SAR,China

出　　处：《Asian Journal of Andrology》2024年第2期165-174,共10页亚洲男性学杂志（英文版）

基　　金：supported by the Shenzhen Science and Technology Program,China(No.KQTD20190929172749226).

摘　　要：Meiosis is the process of producing haploid gametes through a series of complex chromosomal events and the coordinated action of various proteins.The mitochondrial protease complex(ClpXP),which consists of caseinolytic mitochondrial matrix peptidase X(ClpX)and caseinolytic protease P(ClpP)and mediates the degradation of misfolded,damaged,and oxidized proteins,is essential for maintaining mitochondrial homeostasis.ClpXP has been implicated in meiosis regulation,but its precise role is currently unknown.In this study,we engineered an inducible male germ cell-specific knockout caseinolytic mitochondrial matrix peptidase X(Clpx^(cKO))mouse model to investigate the function of ClpX in meiosis.We found that disrupting Clpx in male mice induced germ cell apoptosis and led to an absence of sperm in the epididymis.Specifically,it caused asynapsis of homologous chromosomes and impaired meiotic recombination,resulting in meiotic arrest in the zygotene-to-pachytene transition phase.The loss of ClpX compromised the double-strand break(DSB)repair machinery by markedly reducing the recruitment of DNA repair protein RAD51 homolog 1(RAD51)to DSB sites.This dysfunction may be due to an insufficient supply of energy from the aberrant mitochondria in Clpx^(cKO) spermatocytes,as discerned by electron microscopy.Furthermore,ubiquitination signals on chromosomes and the expression of oxidative phosphorylation subunits were both significantly attenuated in Clpx^(cKO) spermatocytes.Taken together,we propose that ClpX is essential for maintaining mitochondrial protein homeostasis and ensuring homologous chromosome pairing,synapsis,and recombination in spermatocytes during meiotic prophase I.

关 键 词：ClpX homologous chromosome MEIOSIS MITOCHONDRIAL recombination SYNAPSIS 

分 类 号：R697[医药卫生—泌尿科学]