title: HSP60, Bax, apoptosis and the heart.
abstract: HSP60 has primarily been known as a mitochondrial protein that is important for folding key proteins after import into the mitochondria. It is now clear that a significant amount of HSP60 is also present in the extra-mitochondrial cytosol of many cells. In the heart, this cytosolic HSP60 complexes with Bax, Bak and Bcl-XL, but not with Bcl-2. Reduction in HSP60 expression precipitates apoptosis, but does not alter mitochondrial function. During hypoxia, HSP60 cellular distribution changes, with HSP60 leaving the cytosol, and translocating to the plasma membrane. Total cellular HSP60 does not change until 10 h of reoxygenation; however, release of cytochrome c from the mitochondria occurs prior to reoxygenation, coinciding with the redistribution of HSP60. The changes in HSP60, Bax and cytochrome c during hypoxia can be replicated by ATP depletion. HSP60 has also been shown to accelerate the cleavage of pro-caspase3. Thus, HSP60 has a complex role in apoptosis in the cell. Its binding to Bax under normal conditions suggests a key regulatory role in apoptosis.
authors.affiliation: Molecular and Cellular Cardiology, Department of Medicine, University of California, Davis, CA 95616, USA.
authors.forename: S
authors.initials: S
authors.lastname: Gupta
authors.forename: A A
authors.initials: AA
authors.lastname: Knowlton
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D020169:Caspases / Q000378:metabolism; D015687:Cell Hypoxia; D018834:Chaperonin 60 / Q000378:metabolism* / Q000648:ultrastructure; D003574:Cytochrome c Group / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D018834:Chaperonin 60; D003574:Cytochrome c Group; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C076615:cytochrome c''; D020169:Caspases