Mitochondria and aging: a role for the permeability transition?

Abstract

When mitochondria are subjected to oxidative stress and relatively high [Ca2+], they undergo a "permeability transition" in which the inner membrane becomes freely permeable to low-molecular-weight solutes. This phenomenon reflects reversible deformation of the adenine nucleotide translocase, the loss of its native gating properties and the stabilization of the deformed state by cyclophilin-D. The permeability transition may be a factor in cell dysfunction associated with aging. This can manifest in a number of ways ranging, in the most severe, from impaired energy transduction and compromised viability to more subtle influences on the propagation of Ca2+ signals. This article critically examines data relevant to this issue.