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Quantitative biochemical and ultrastructural comparison of mitochondrial permeability transition in isolated brain and liver mitochondria: evidence for reduced sensitivity of brain mitochondria.

Abstract：

:Opening of the mitochondrial permeability transition pore has increasingly been implicated in excitotoxic, ischemic, and apoptotic cell death, as well as in several neurodegenerative disease processes. However, much of the work directly characterizing properties of the transition pore has been performed in isolated liver mitochondria. Because of suggestions of tissue-specific differences in pore properties, we directly compared isolated brain mitochondria with liver mitochondria and used three quantitative biochemical and ultrastructural measurements of permeability transition. We provide evidence that brain mitochondria do not readily undergo permeability transition upon exposure to conditions that rapidly induce the opening of the transition pore in liver mitochondria. Exposure of liver mitochondria to transition-inducing agents led to a large, cyclosporin A-inhibitable decrease in spectrophotometric absorbance, a loss of mitochondrial glutathione, and morphologic evidence of matrix swelling and disruption, as expected. However, we found that similarly treated brain mitochondria showed very little absorbance change and no loss of glutathione. The absence of response in brain was not simply due to structural limitations, since large-amplitude swelling and release of glutathione occurred when membrane pores unrelated to the transition pore were formed. Additionally, electron microscopy revealed that the majority of brain mitochondria appeared morphologically unchanged following treatment to induce permeability transition. These findings show that isolated brain mitochondria are more resistant to induction of permeability transition than mitochondria from liver, which may have important implications for the study of the mechanisms involved in neuronal cell death.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Berman SB,Watkins SC,Hastings TG

doi

10.1006/exnr.2000.7438

keywords:

subject

Has Abstract

pub_date

2000-08-01 00:00:00

pages

415-25

issue

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(00)97438-7

journal_volume

164

pub_type

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Quantitative biochemical and ultrastructural comparison of mitochondrial permeability transition in isolated brain and liver mitochondria: evidence for reduced sensitivity of brain mitochondria.