The mitochondrial permeability transition: The brain's point of view

Janet M. Dubinsky, Nickolay Brustovetsky, Vsevolod Pinelis, Bruce S. Kristal, Carter Herman, Xinren Li

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

The mitochondrial permeability transition (mPT) has been implicated in both central nervous system ischaemia/reperfusion injury and excitotoxic neuronal death. To characterize the mPT of brain mitochondria, fluorescent mitochondrial dyes were applied to cultured neurons and astrocytes and isolated brain mitochondria were prepared. In astrocytes, mPT induction was observed as calcium-induced mitochondrial swelling following permeabilization by digitonin or introduction of a calcium ionophore. In hippocampal neurons, mPT induction was observed upon introduction of calcium and ionophore or application of toxic doses of glutamate. In isolated brain mitochondria, calcium dose-dependently produced calcium accumulation and mitochondrial swelling that was prevented by pretreatment with ADP or cyclosporin A. Additionally, when mitochondrial substrates were limited, calcium dose-dependently produced mitochondrial depolarization without swelling or calcium accumulation that was reversed by ADP, cyclosporin A or Ruthenium Red. The degree of mitochondrial depolarization was modulated by free fatty acids, magnesium, calcium concentration and protonophore Repolarization of mitochondria and closure of this low-conductance manifestation of the mPT pore by cyclosporin A was modulated by the degree of depolarization.

Original languageEnglish (US)
Pages (from-to)75-84
Number of pages10
JournalBiochemical Society Symposium
Volume66
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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