Mitochondrial membrane potential in aging cells

Mary M. Sugrue, William G. Tatton

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Decreased mitochondrial membrane potential (ΔπM) has been found in a variety of aging cell types from several mammalian species. The physiological significance and mechanisms of the decreased ΔπMin aging are not well understood. This review considers the generation of ΔπMand its role in ATP generation together with factors that modify ΔπMwith emphasis on mitochondrial membrane permeability, particularly the role of a multiprotein membrane megapore, the mitochondrial permeability transition pore complex (PTPC). Previous data showing decreased ΔπMin aged cells is considered in relation to the methods available to estimate ΔπM. In the past the majority of studies used whole cell rhodamine 123 fluorescence to estimate ΔπMin lymphocytes from mice or rats. Imaging of ΔπMin living, in situ mitochondria using laser confocal scanning microscopy offers advantages over whole cell measurements or those from isolated mitochondria, particularly if several different potentiometric dyes are employed. Furthermore, high resolution imaging of the newer fixable potentiometric dyes allows immunocytochemistry for specific proteins and ΔπMto be examined in the same cells or even the same mitochondria. We found that decreased ΔπMin p53 overexpression-induced or naturally occurring senescence is associated with decreased responsiveness of the PTPC to agents that induce either its opening or closing. The decreased PTPC responsiveness seems to reflect, at least in part, decreased levels of a key PTPC protein, the adenine nucleotide translocase. We also consider the possible basis for decreased ΔπMin fibroblasts from patients with Parkinsons disease, an age-related neurodegenerative disease. Finally, we speculate on the mechanisms and functional significance of decreased ΔπMin aging.

Original languageEnglish
Pages (from-to)176-188
Number of pages13
JournalNeuroSignals
Volume10
Issue number3-4
DOIs
StatePublished - 24 May 2001

Keywords

  • Adenine nucleotide translocase
  • Aging
  • Chloromethyl-tetramethylrosamine methyl ester
  • Mitochondrial membrane potential (ΔΨ)
  • Senescence

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