PT  - JOURNAL ARTICLE
AU  - Wang, Mei
AU  - Zeng, Ling
AU  - Xiong, Yao
AU  - Wang, Xiao-fei
AU  - Cheng, Lin
AU  - Wang, Fang
AU  - Su, Ping
AU  - Zhang, Yuan-zhen
TI  - NF-κB-repressed Sirt3 mediates testicular cholesterol metabolism and cytoskeleton assembly via P450scc/SOD2 deacetylation during spermatogenesis
AID  - 10.1101/2021.02.22.432399
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.02.22.432399
4099  - http://biorxiv.org/content/early/2021/02/23/2021.02.22.432399.short
4100  - http://biorxiv.org/content/early/2021/02/23/2021.02.22.432399.full
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