Confocal microscopy of the mitochondrial permeability transition in necrotic cell killing, apoptosis and autophagy

John J. Lemasters, Ting Qian, Steven P. Elmore, Lawrence C. Trost, Yoshiya Nishimura, Brian Herman, Cynthia A. Bradham, David A. Brenner, Anna Liisa Nieminen

Research output: Contribution to journalShort surveypeer-review

63 Scopus citations

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, Ca2+ ionophore toxicity and tumor necrosis factor alpha (TNFα) induced apoptosis, and may contribute to Reye's-related drag toxicity. Pyridine nucleotide oxidation, mitochondrial generation of reactive oxygen species, and increased mitochondrial Ca2+ and pH can each promote onset of the MPT in situ. The MPT can also be directly visualized during TNFα-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.

Original languageEnglish (US)
Pages (from-to)283-285
Number of pages3
JournalBioFactors
Volume8
Issue number3-4
DOIs
StatePublished - 1998

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