Cytosolic Accumulation of HSP60 during Apoptosis with or without Apparent Mitochondrial Release
Year: 2007
Type: article
Abstract: Most heat shock proteins (HSPs) have pro-survival functions. However, the role of HSP60, a mitochondrial matrix protein, is somewhat controversial with both pro-survival and pro-apoptotic functions reported. Here we show that in numerous apoptotic systems HSP60 protein accumulates in the cytosol. In BMD188-induced cell death, HSP60 accumulates in the cytosol with significant mitochondrial release. In contrast, in apoptosis induced by multiple other inducers, the cytosolic HSP60 accumulates without an apparent mitochondrial release. The short interfering RNA-mediated knockdown experiments revealed that in BMD188-induced apoptosis, HSP60 has a pro-death function and that the pro-death role of HSP60 seems to involve caspase-3 maturation and activation in the cytosol. In contrast, HSP60 appears to play a pro-survival role in other apoptotic systems where there is no apparent mitochondrial release as its knockdown promotes cell death. In these latter apoptotic systems HSP60 does not associate with active caspase-3. In both cases, HSP60 does not appreciably interact with Bax. Taken together, our results suggest the following: 1) cytosolic accumulation of HSP60 represents a common phenomenon during apoptosis induction; 2) cytosolic HSP60 accumulation during apoptosis occurs either with or without apparent mitochondrial release; and 3) the cytosolically accumulated HSP60 possesses either pro-survival or pro-death functions, which involves differential interactions with caspase-3.
Source: Journal of Biological Chemistry
Authors: Dhyan Chandra, Grace Choy, Dean G. Tang
Institution: The University of Texas MD Anderson Cancer Center
Language: English
Topic: Heat shock proteins research
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Awards: Novel Insight on Nucleotide Regulation of Apoptosome Activation, G1592235300, G1653363916, Nucleotide Regulation of Apaf-1 Apoptosome and Apoptosis, 15-Lipoxygenase 2 is a Prostate Senescence Gene, G2630018723, G4003081979, G4119534169, NANOG AS A CRITICAL PROSTATE CANCER (STEM CELL) SELF-RENEWAL GENE, Mechanisms and Prevention of Environmental Disease, G5660809884, G5850682332, G9000072347, G9000325578
OpenAlex ID: W2092485963