Affiliations: Department of Cell Biology and Anatomy, University of North Carolina, Chapel Hill, NC, USA | Department of Medicine, University of North Carolina, Chapel Hill, NC, USA | Department of Anatomy, Case Western Reserve University, Cleveland, OH, USA
Note: [] Send correspondence to: Dr. John J. Lemasters, Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill, CB #7090, 236 Taylor Hall, Chapel Hill, NC 27599‐7090, USA.
Abstract: Onset of the cyclosporin‐A‐sensitive mitochondrial permeability transition (MPT) in individual mitochondria within living cells can be visualized by laser scanning confocal microscopy. The MPT is a causative event in many types of necrotic and apoptotic cell death, including oxidative stress, ischemia/reperfusion injury, Ca^{2+} ionophore toxicity and tumor necrosis factor alpha (TNF\alpha) induced apoptosis, and may contribute to Reye’s‐related drug toxicity. Pyridine nucleotide oxidation, mitochondrial generation of reactive oxygen species, and increased mitochondrial Ca^{2+} and pH can each promote onset of the MPT in situ. The MPT can also be directly visualized during TNF\alpha‐induced apoptosis to hepatocytes. Mitochondria spontaneously depolarize in situ after nutrient deprivation before entering an acidic lysosomal compartment, suggesting that the MPT precedes the normal process of mitochondrial autophagy. We propose a model in which onset of the MPT to increasing numbers of mitochondria leads progressively to autophagy, apoptosis and necrotic cell death.
Journal: Biofactors, vol. 8, no. 3-4, pp. 283-285, 1998
