Reduced mitochondrial membrane potential and altered responsiveness of a mitochondrial membrane megachannel in p53-induced senescence

Mary M. Sugrue, Yan Wang, Hardy J. Rideout, Ruth M.E. Chalmers-Redman, William G. Tatton

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

There is accumulating evidence that mitochondrial membrane potential (ΔΨ(M)) is reduced in aged cells. In addition, a decrease of ΔΨ(M) has been shown to be an early event in many forms of apoptosis. Here we use a mitochondrial potentiometric dye with in situ laser scanning confocal microscopic (LSCM) imaging to demonstrate that ΔΨ(M) is dramatically decreased in both the p53-overexpressing, senescent EJ tumor cells and in pre-apoptotic PC12 cells compared to controls. Treatment with cyclosporin A (CSA), which facilitates closure of the mitochondrial permeability transition pore (PTP), was able to reverse the decrease in ΔΨ(M) in pre-apoptotic PC12 cells but not in the senescent EJ-p53 cells. The capacity to prevent dissipation of ΔΨ(M) in response to agents that facilitate PTP closure may differentiate cells entering apoptosis from those participating in senescence. Therefore, regulation of the closure of the mitochondrial PTP in the presence of decreased ΔΨ(M) may be a decisional checkpoint in distinguishing between growth arrest pathways.

Original languageEnglish
Pages (from-to)123-130
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume261
Issue number1
DOIs
StatePublished - 22 Jul 1999

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