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The Identity and Regulation of the Mitochondrial Permeability Transition Pore
Author(s) -
Juhaszova Magdalena,
Wang Su,
Zorov Dmitry B.,
Bradley Nuss H.,
Gleichmann Marc,
Mattson Mark P.,
Sollott Steven J.
Publication year - 2008
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1420.023
Subject(s) - voltage dependent anion channel , mitochondrial permeability transition pore , microbiology and biotechnology , adenine nucleotide translocator , mitochondrion , biophysics , nuclear pore , regulator , biology , chemistry , biochemistry , cytoplasm , programmed cell death , bacterial outer membrane , gene , apoptosis , escherichia coli
The mitochondrial permeability transition (MPT) pore complex is a key participant in the machinery that controls mitochondrial fate and, consequently, cell fate. The quest for the pore identity has been ongoing for several decades and yet the main structure remains unknown. Established “dogma” proposes that the core of the MPT pore is composed of an association of voltage‐dependent anion channel (VDAC) and adenine nucleotide translocase (ANT). Recent genetic knockout experiments contradict this commonly accepted interpretation and provide a basis for substantial revision of the MPT pore identity. There is now sufficient evidence to exclude VDAC and ANT as the main pore structural components. Regarding MPT pore regulation, the role of cyclophilin D is confirmed and ANT may still serve some regulatory function, although the involvement of hexokinase II and creatine kinase remains unresolved. When cell protection signaling pathways are activated, we have found that the Bcl‐2 family members relay the signal from g lycogen synthase kinase‐3 beta onto a target at or in close proximity to the pore. Our experimental findings in intact cardiac myocytes and neurons indicate that the current “dogma” related to the role of Ca 2+ in MPT induction requires reevaluation. Emerging evidence suggests that after injury‐producing stresses, reactive oxygen species (but not Ca 2+ ) are largely responsible for the pore induction. In this article we discuss the current state of knowledge and provide new data related to the MPT pore structure and regulation.