Mitochondrial nucleoid remodeling and biogenesis are regulated by the p53-p21^WAF1-PKCζ pathway in p16^INK4a-silenced cells.

ABSTRACT: Mitochondrial dysfunction is linked to age-related senescence phenotypes. We report here the pathway increasing nucleoid remodeling and biogenesis in mitochondria during the senescence of foreskin human diploid fibroblasts (fs-HDF) and WI-38 cells. Replicative senescence in fs-HDF cells increased mitochondrial nucleoid remodeling as indicated by 5-bromo-2'-deoxyuridine (BrdU) incorporation and mitochondrial transcription factor A (TFAM) expression in enlarged and fused mitochondria. Mitochondrial nucleoid remodeling was accompanied by mitochondrial biogenesis in old cells, and the expression levels of OXPHOS complex-I, -IV and -V subunits, PGC-1α and NRF1 were greatly increased compared to young cells. Activated protein kinase C zeta (PKCζ) increased mitochondrial activity and expressed ph

SUBMITTER: Lee YY 

PROVIDER: S-EPMC7202532 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature