Mitochondrial stress-induced p53 attenuates HIF-1α activity by physical association and enhanced ubiquitination.

ABSTRACT: Retrograde signaling is a mechanism by which mitochondrial dysfunction is communicated to the nucleus for inducing a metabolic shift essential for cell survival. Previously, we showed that partial mitochondrial DNA (mtDNA) depletion in different cell types induced mitochondrial retrograde signaling pathway (MtRS) involving Ca⁺²-sensitive Calcineurin (Cn) activation as an immediate upstream event of stress response. In multiple cell types, this stress signaling was shown to induce tumorigenic phenotypes in immortalized cells. In this study we show that MtRS also induces p53 expression, which was abrogated by Ca²⁺ chelators and short hairpin RNA-mediated knockdown of CnAβ mRNA. Mitochondrial dysfunction induced by mitochondrial ionophore, carbonyl cyanide m-chlorophenyl

SUBMITTER: Chowdhury AR 

PROVIDER: S-EPMC5192009 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature