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Myocardial subsarcolemmal and intermyofibrillar mitochondria respond differently to apoptotic stimuli
Author(s) -
Kavazis Andreas N,
McClung Joseph M,
Hood David A,
Powers Scott K
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb92-c
Subject(s) - mitochondrion , cytochrome c , mitochondrial apoptosis induced channel , apoptosis , voltage dependent anion channel , microbiology and biotechnology , mitochondrial permeability transition pore , reactive oxygen species , chemistry , oxidative phosphorylation , cytochrome c oxidase , biology , biochemistry , programmed cell death , bacterial outer membrane , escherichia coli , gene
Reactive oxygen species (ROS) can trigger apoptosis by increasing permeability of the mitochondrial permeability transition pore (mtPTP) leading to release of the proapoptotic factors cytochrome c and apoptosis‐inducing factor (AIF). Two subpopulations of mitochondria exist in cardiac muscle, but it is unknown if these mitochondrial subpopulations differ in their susceptibility to apoptotic stimuli. Therefore, we investigated the susceptibility of cardiac subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondrial subfractions to apoptosis‐induced oxidative stress. Basal protein levels of key mtPTP components (voltage‐dependent anion channel 1, adenine nucleotide translocase, and cyclophilin D) were higher in SS compared to IMF mitochondria. In response to apoptotic stimuli, IMF mitochondria exhibit a higher rate of mtPTP opening (Vmax), but time required to reach Vmax was shorter for SS mitochondria. Exposure to ROS induced an increase in cytochrome c and AIF release from IMF mitochondria, but did not alter release in SS mitochondria. We conclude that cardiac muscle SS and IMF mitochondria differentially respond to apoptotic stimuli. Supported by National Institutes of Health grant R01HL067855 awarded to S.K. Powers.