On the Involvement of Mitochondrial Intermembrane Junctional Complexes in Apoptosis

Author(s): Martin Crompton.

Journal Name: Current Medicinal Chemistry

Volume 10 , Issue 16 , 2003

Abstract:

The voltage dependent anion channel and the adenine nucleotide translocase are the principal proteins found in the mitochondrial outer and inner membranes, respectively. The two proteins can associate to form a junctional complex that establishes contact sites between the two membranes. This complex in turn recruits a range of proteins depending on the function to be executed. Among these, the junctional complexes can bind Bax and other proapoptotic proteins. Bax regulates the involvement of mitochondria in the apoptotic signalling pathway by controlling the the release of apoptogenic proteins from the mitochondrial intermembrane space to the cytosol. Another protein recruited to ANT is cyclophilin-D. Cyclophilin-D is a peptidylprolyl cis-trans-isomerase located in the intramitochondrial (matrix) compartment which stabilizes a “deformed” conformation of ANT in which its native gating properties are lost. Although the deformed state, when extensive, is lethal, cells can tolerate this conformational change when it occurs transiently. There is now a large body of data that implicates the voltage dependent anion channel, the adenine nucleotide translocase and cyclophilin-D, both separately and together, in the mitochondrial reactions of apoptosis. But there is no consensus over how, or indeed if, they are involved. This article examines the data relevant to this question and considers why a complex of these three proteins may be essential for the action of Bax and other proapoptotic proteins in permeabilizing the outer membrane to intermembrane space proteins.

Keywords: mitochondrial intermembrane, junctional complexes, voltage dependent anion channel, adenine nucleotide translocase, cyclophilin-D, peptidylprolyl cis-trans-isomerase, intramitochondrial (matrix) compartment

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Article Details

VOLUME: 10
ISSUE: 16
Year: 2003
Page: [1473 - 1484]
Pages: 12
DOI: 10.2174/0929867033457197
Price: $58

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