RT Journal Article
SR Electronic
T1 NF-κB-repressed Sirt3 mediates testicular cholesterol metabolism and cytoskeleton assembly via P450scc/SOD2 deacetylation during spermatogenesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.22.432399
DO 10.1101/2021.02.22.432399
A1 Wang, Mei
A1 Zeng, Ling
A1 Xiong, Yao
A1 Wang, Xiao-fei
A1 Cheng, Lin
A1 Wang, Fang
A1 Su, Ping
A1 Zhang, Yuan-zhen
YR 2021
UL http://biorxiv.org/content/early/2021/02/23/2021.02.22.432399.abstract
AB Testicular homeostasis requires the balanced interplay between specific molecules in Sertoli cells, Leydig cells, germ cells. Loss of this coordination can lead to the disruption of spermatogenesis, even male infertility. By operating the upregulation and downregulation of Sirt3 in our male subfertility rats model and two testicular cells models, we indicated that Sirt3 overexpression and activator ameliorated cholesterol metabolism via P450scc deacetylation in Leydig cells, and cytoskeleton assembly via PDLIM1 with SOD2 deacetylation in Sertoli cells and elongating spermatids. In terms of the upstream regulator of Sirt3, the phosphorylation of NF-κB p65Ser536 stimulated the nuclear translocation of NF-κB subunits (p50, p65, RelB), which bound to TFBS1 and TFBS2 synchronously in the promoter of Sirt3, repressing Sirt3 transcription. This study demonstrates that NF-κB-repressed SIRT3 acts directly on cholesterol metabolism of Leydig cells and cytoskeleton assembly of Sertoli cells via P450scc/SOD2 deacetylation to regulate sperm differentiation, influencing spermatogenesis, even male fertility.Research organism: Rat, mouse