Mitochondrial import of the human chaperonin (HSP60) protein

Singh, Bhag; Patel, Hasmukh V.; Ridley, Robert G.; Freeman, Karl B.; Gupta, Radhey S.

doi:10.1016/0006-291x(90)90344-m

Cited by 64 publications

(30 citation statements)

References 21 publications

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“…Cytosolic HSP60 (cHSP60) can be found in 2 forms, namely, with or without the mitochondrial signal sequence, a sort of "tail" that the molecule, translated in the cytosol, loses when it enters into this organelle [29]. It is not clear if cHSP60 forms the same heptameric structure, i.e.…”

Section: Hsp60 Has Anti-apoptotic Effects In Cardio-myocytesmentioning

confidence: 99%

Heat Shock Protein-60 and Risk for Cardiovascular Disease

Rizzo¹,

Macario²,

Macario³

et al. 2011

CPD

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Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. There is growing evidence that molecular chaperones, many of which are heat shock proteins HSPs, are involved in CVD pathogenesis. In this review we focus on HSP60, the human mitochondrial chaperone that also displays extramitochondrial and extracellular functions. HSP60 is typically cytoprotective but a number of stress conditions determine its conversion to a potentially toxic molecule for cells and tissues. We present illustrative examples of specific subtypes of CVD where HSP60 is implicated in the initiation and/or progression of disease. The data not only indicate a pathogenic role for HSP60 but also its potential as a biomarker with applications for diagnosis, assessing prognosis and response to treatment, as well as for preventing and treating CVD.

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Section: Hsp60 Has Anti-apoptotic Effects In Cardio-myocytesmentioning

confidence: 99%

Heat Shock Protein-60 and Risk for Cardiovascular Disease

Rizzo¹,

Macario²,

Macario³

et al. 2011

CPD

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“…Thus there was a preferential increase in HSP60 alone, rather than an increase in total mitochondrial protein. HSP60 is thought to be synthesized in the cytosol from a nuclear transcript as a pre-HSP60 with a 26-amino acid mitochondrial transport sequence (MTS) at the amino terminus (19). After transport to the mitochondria, the MTS is cleaved and some of the HSP60 returns to the cytosol (19).…”

Section: Hsp60 Distribution In Heart Failurementioning

confidence: 99%

“…HSP60 is thought to be synthesized in the cytosol from a nuclear transcript as a pre-HSP60 with a 26-amino acid mitochondrial transport sequence (MTS) at the amino terminus (19). After transport to the mitochondria, the MTS is cleaved and some of the HSP60 returns to the cytosol (19). The presence of this 26-amino acid (molecular mass 3.1 kDa) MTS was clearly distinguished from cleaved HSP60 by 10% SDS-PAGE (19).…”

Section: Hsp60 Distribution In Heart Failurementioning

confidence: 99%

HSP60 in heart failure: abnormal distribution and role in cardiac myocyte apoptosis

Li¹,

Kim²,

Wang³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

137

124

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Amione G, Knowlton AA. HSP60 in heart failure: abnormal distribution and role in cardiac myocyte apoptosis. Am J Physiol Heart Circ Physiol 293: H2238-H2247, 2007. First published August 3, 2007; doi:10.1152/ajpheart.00740.2007.-Heat shock protein (HSP) 60 is a mitochondrial and cytosolic protein. Previously, we reported that HSP60 doubled in end-stage heart failure, even though levels of the protective HSP72 were unchanged. Furthermore, we observed that acute injury in adult cardiac myocytes resulted in movement of HSP60 to the plasma membrane. We hypothesized that the inflammatory state of heart failure would cause translocation of HSP60 to the plasma membrane and that this would provide a pathway for cardiac injury. Two models were used to test this hypothesis: 1) a rat model of heart failure and 2) human explanted failing hearts. We found that HSP60 localized to the plasma membrane and was also found in the plasma early in heart failure. Plasma membrane HSP60 localized to lipid rafts and was detectable on the cell surface with the use of both flow cytometry and confocal microscopy. Localization of HSP60 to the cell surface correlated with increased apoptosis. In heart failure, HSP60 is in the plasma membrane fraction, on the cell surface, and in the plasma. Membrane HSP60 correlated with increased apoptosis. Release of HSP60 may activate the innate immune system, promoting a proinflammatory state, including an increase in TNF-␣. Thus abnormal trafficking of HSP60 to the cell surface may be an early trigger for myocyte loss and the progression of heart failure.heat shock proteins; protein trafficking; plasma membrane; cytokines HSP60 IS AN IMPORTANT MEMBER of the heat shock protein family, thought to be primarily a mitochondrial protein, although it is encoded by the nuclear genome. Previously, our laboratory (8) reported that HSP60 is doubled in end-stage heart failure. HSP60 binds Bax and Bak in the cytosol of the myocyte, and reduction in HSP60 precipitates apoptosis (6). Simulated ischemia in cardiac myocytes resulted in translocation of HSP60 to the plasma membrane before reoxygenation (5). Redistribution of HSP60 to the plasma membrane was associated with movement of Bax to the mitochondria and apoptosis.Observations of HSP60 translocation in isolated myocytes motivated studies on the redistribution of HSP60 in the failing heart, where apoptosis is thought to be a mechanism of myocyte death. To address this question, we developed a rat model of heart failure with ligation of the left anterior descending artery. Cardiac echo was used to follow changes in function and chamber size. Studies were conducted long after coronary ligation and thus reflected the progressive changes of the failing ventricle, rather than ischemia. Upregulation of HSP60 correlated with increased expression of proinflammatory cytokines, brain natriuretic peptide (BNP), and atrial natriuretic peptide (ANP) 9 and 12 wk postligation. In addition, we examined distribution of HSP60 in explanted human hearts with dilated (DCM) and ischem...

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“…In eukaryotes, Hsp60 has been thought to be present and to function in protein folding only in organelles such as mitochondria and chloroplasts (Cheng et al 1989;Roy 1989;Ellis and van der Vies 1991;Zeilstra-Ryalls et al 1991;Craig et al 1993), which are of endosymbiotic origin (Portier 1918;Wallin 1925;Margulis 1970;Gray 1992). Hsp60 is encoded by nuclear DNA (Jindal et al 1989;Picketts et al 1989;Reading et al 1989) and is synthesized as a larger precursor form containing an N-terminal targeting sequence which is necessary for its mitochondrial import and is cleaved during maturation to the mature form in the mitochondrial matrix (Jindal et al 1989;Singh et al 1990). However, a variety of biochemical, immunological, and subcellular localization data have raised the possiblity that Hsp60 as a molecular chaperone may be essential for the biological functioning of other proteins at unexpected extramitochondrial locations (Soltys and Gupta 1999a,b,c).…”

mentioning

confidence: 99%

Localization of Mitochondrial 60-kD Heat Shock Chaperonin Protein (Hsp60) in Pituitary Growth Hormone Secretory Granules and Pancreatic Zymogen Granules

Cechetto

Soltys

Gupta

2000

J Histochem Cytochem.

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SUMMARYWe used quantitative immunogold electron microscopy and biochemical analysis to evaluate the subcellular distribution of Hsp60 in rat tissues. Western blot analysis, employing both monoclonal and polyclonal antibodies raised against mammalian Hsp60, shows that only a single 60-kD protein is reactive with the antibodies in brain, heart, kidney, liver, pancreas, pituitary, spleen, skeletal muscle, and adrenal gland. Immunogold labeling of tissues embedded in the acrylic resin LR Gold shows strong labeling of mitochondria in all tissues. However, in the anterior pitutary and in pancreatic acinar cells, Hsp60 also localizes in secretory granules. The labeled granules in the pituitary and pancreas were determined to be growth hormone granules and zymogen granules, respectively, using antibodies to growth hormone and carboxypeptidase A. Immunogold labeling of Hsp60 in all compartments was prevented by preadsorption of the antibodies with recombinant Hsp60. Biochemically purified zymogen granules free of mitochondrial contamination are shown by Western blot analysis to contain Hsp60, confirming the morphological localization results in pancreatic acinar cells. In kidney distal tubule cells, low Hsp60 reactivity is associated with infoldings of the basal plasma membrane. In comparison, the plasma membrane in kidney proximal tubule cells and in other tissues examined showed only background labeling. These findings raise interesting questions concerning translocation mechanisms and the cellular roles of Hsp60.

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Mitochondrial import of the human chaperonin (HSP60) protein

Cited by 64 publications

References 21 publications

Heat Shock Protein-60 and Risk for Cardiovascular Disease

Heat Shock Protein-60 and Risk for Cardiovascular Disease

HSP60 in heart failure: abnormal distribution and role in cardiac myocyte apoptosis

Localization of Mitochondrial 60-kD Heat Shock Chaperonin Protein (Hsp60) in Pituitary Growth Hormone Secretory Granules and Pancreatic Zymogen Granules

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