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Your search keyword '"p16INK4a silence"' showing total 2 results
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2 results on '"p16INK4a silence"'

1. Mitochondrial nucleoid remodeling and biogenesis are regulated by the p53-p21

Author

Yun Yeong, Lee, Yeon Seung, Choi, Do Wan, Kim, Jae Youn, Cheong, Kye Yong, Song, Min Sook, Ryu, and In Kyoung, Lim

Subjects
Cyclin-Dependent Kinase Inhibitor p21, senescence, Protein Serine-Threonine Kinases, DNA, Mitochondrial, Oxidative Phosphorylation, Mitochondrial Proteins, nucleoid remodeling, AMP-Activated Protein Kinase Kinases, p53-p21-PKCζ activation, Humans, Topoisomerase II Inhibitors, Gene Silencing, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, Protein Kinase C, Organelle Biogenesis, Nuclear Respiratory Factor 1, Fibroblasts, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, p16INK4a silence, Mitochondria, DNA-Binding Proteins, mitochondria, Doxorubicin, Tumor Suppressor Protein p53, Signal Transduction, Transcription Factors, Research Paper
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 phenotypes of delayed senescence in fs-HDF cells, but not in WI-38 cells. The findings were reproduced in the doxorubicin-induced senescence of young fs-HDF and WI-38 cells via the PKCζ-LKB1-AMPK signaling pathway, which was regulated by the p53-p21WAF1 pathway when p16INK4a was silenced. The signaling enhanced PGC-1α-NRF1-TFAM axis in mitochondria, which was demonstrated by Ingenuity Pathway Analysis of young and old fs-HDF cells. Activation of the p53-p21WAF1 pathway and silencing of p16INK4a are responsible for mitochondrial reprogramming in senescent cells, which may be a compensatory mechanism to promote cell survival under senescence stress.

Published
2019

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

Author

Lee YY, Choi YS, Kim DW, Cheong JY, Song KY, Ryu MS, and Lim IK

Subjects
AMP-Activated Protein Kinase Kinases, Cyclin-Dependent Kinase Inhibitor p16 genetics, Cyclin-Dependent Kinase Inhibitor p21 genetics, Cyclin-Dependent Kinase Inhibitor p21 metabolism, DNA, Mitochondrial metabolism, DNA-Binding Proteins metabolism, Doxorubicin pharmacology, Fibroblasts metabolism, Gene Silencing, Humans, Mitochondrial Proteins metabolism, Nuclear Respiratory Factor 1 metabolism, Oxidative Phosphorylation, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha metabolism, Protein Kinase C metabolism, Protein Serine-Threonine Kinases metabolism, Signal Transduction, Topoisomerase II Inhibitors pharmacology, Transcription Factors metabolism, Tumor Suppressor Protein p53 metabolism, Cellular Senescence drug effects, DNA-Binding Proteins genetics, Mitochondria genetics, Mitochondria metabolism, Mitochondrial Proteins genetics, Organelle Biogenesis, Transcription Factors genetics
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 phenotypes of delayed senescence in fs-HDF cells, but not in WI-38 cells. The findings were reproduced in the doxorubicin-induced senescence of young fs-HDF and WI-38 cells via the PKCζ-LKB1-AMPK signaling pathway, which was regulated by the p53-p21 WAF1 pathway when p16 INK4a was silenced. The signaling enhanced PGC-1α-NRF1-TFAM axis in mitochondria, which was demonstrated by Ingenuity Pathway Analysis of young and old fs-HDF cells. Activation of the p53-p21 WAF1 pathway and silencing of p16 INK4a are responsible for mitochondrial reprogramming in senescent cells, which may be a compensatory mechanism to promote cell survival under senescence stress.

Published
2020
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