Cytosolic Hsp60 Can Modulate Proteasome Activity in Yeast

Kalderon, Bella; Kogan, Gleb; Bubis, Ettel; Pines, Ophry

doi:10.1074/jbc.m114.626622

Cited by 29 publications

(27 citation statements)

References 43 publications

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“…In a yeast system, it has been found that cytosolic HSP60 can stabilize Bax to enhance its association with mitochondria so that its pro-apoptotic effect is raised. In this model, it has also been found that cytosolic HSP60 physically interacts with proteasome to inhibit its activities, accompanied by the generation of an increased amount of polyubiquitinated proteins [39].…”

Section: Dual Functions Of Hsp60 In Cytosolmentioning

confidence: 95%

“…In the study by Kalderon et al, cytosolic HSP60 is capable of regulating proteasome activity in yeast. Elevation of cytosolic HSP60 induces the accumulation of polyubiquitinated proteins [39]. During death stimuli, increased cytosolic HSP60 due to mitochondrial release exerts a pro-apoptotic function in cells.…”

Section: Interaction Between Hsp60 and Survivin In Cytosolmentioning

confidence: 99%

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Functional Compartmentalization of HSP60-Survivin Interaction between Mitochondria and Cytosol in Cancer Cells

Huang

Yeh

2019

Cells

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Heat shock protein 60 (HSP60) and survivin reside in both the cytosolic and mitochondrial compartments under physiological conditions. They can form HSP60-survivin complexes through protein-protein interactions. Their expression levels in cancer tissues are positively correlated and higher expression of either protein is associated with poor clinical prognosis. The subcellular location of HSP60-survivin complex in either the cytosol or mitochondria is cell type-dependent, while the biological significance of HSP60-survivin interaction remains elusive. Current knowledge indicates that the function of HSP60 partly rests on where HSP60-survivin interaction takes place. HSP60 has a pro-survival function when binding to survivin in the mitochondria through interacting with other factors such as CCAR2 and p53. In response to cell death signals, mitochondrial survivin functions through preventing procaspase activation. Degradation of cytosolic survivin leads to the loss of mitochondrial membrane potential and aberrant mitosis processes. On the other hand, HSP60 release from mitochondria to cytosol upon death stimuli might exert a pro-death function, either through stabilizing Bax, enhancing procaspase-3 activation, or increasing protein ubiquitination. Combining the knowledge of mitochondrial HSP60-survivin complex function, cytosolic survivin degradation effect, and pro-death function upon mitochondria release of HSP60, a hypothetical scenario for HSP60-survivin shuttling upon death stimuli is proposed.

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Section: Dual Functions Of Hsp60 In Cytosolmentioning

confidence: 95%

Section: Interaction Between Hsp60 and Survivin In Cytosolmentioning

confidence: 99%

Functional Compartmentalization of HSP60-Survivin Interaction between Mitochondria and Cytosol in Cancer Cells

Huang

Yeh

2019

Cells

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“…It is well-known that intracellular protein degradation is mainly induced by two cellular routes: the ubiquitinproteasome system (UPS) and the autophagy-lysosome system [46]. HSP60 has been reported to modulate proteasome activity and protein ubiquitination [45,47]. We thus investigated the potential effects of HSP60 on the UPS.…”

Section: Hsp60 Knockdown Mitigated the Protective Effects Of Adiponecmentioning

confidence: 99%

Heat shock protein 60 (HSP60) modulates adiponectin signaling by stabilizing adiponectin receptor

et al. 2020

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Adiponectin, an adipokine produced and secreted by adipocytes, is involved in regulating the development and progression of insulin resistance, diabetes, and diabetic complications. Heat shock protein 60 (HSP60) is a molecular chaperone, most commonly presenting in mitochondria and participating in the maintenance of protein homeostasis. Accumulating studies have demonstrated that the elevated circulating HSP60 and the decreased intracellular HSP60 are closely associated with diabetic complications such as diabetic cardiomyopathy. However, the underlying mechanism remains poorly understood. In the present study, we reported that HSP60 interacted directly with adiponectin receptors. Its abundance was positively associated with adiponectin action. Furthermore, HSP60 depletion markedly mitigated the protective impacts of adiponectin on high glucose-induced oxidative stress and cell apoptosis in rat cardiac H9c2 cells. In addition, HSP60 knockdown significantly enhanced proteasome activity leading to the degradation of adiponectin receptor 1. Taken together, we showed for the first time that HSP60 interacted with adiponectin receptors and mediated adiponectin signaling through stabilizing adiponectin receptor. This in vitro study also provides an alternative explanation for mechanism by which adiponectin exerts its action.

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“…This newly identified pathway, which was termed UPRam (unfolded protein response activated by mistargeting of proteins), links defects in mitochondrial biogenesis with proteasome activity, thus buffering the consequences of physiological slowdown in mitochondrial protein import. Interestingly, the mitochondrial chaperone Hsp60 was also recently linked to the proteasome, as localization of Hsp60 to the cytosol was shown to modulate proteasome activity according to cellular needs . As accumulation of Hsp60 in the cytosol resulted in reduced proteasomal activity, it might be that the balance between Hsp60 levels and the levels of untargeted proteins is the signal that transmits the mitochondrial status to the cell and leads to the needed outcome.…”

Section: Signaling From Within Mitochondria To the Nucleusmentioning

confidence: 99%

Ground control to major TOM: mitochondria–nucleus communication

Eisenberg-Bord

Schuldiner

2016

The FEBS Journal

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Mitochondria have crucial functions in the cell, including ATP generation, iron-sulfur cluster biogenesis, nucleotide biosynthesis, and amino acid metabolism. All of these functions require tight regulation on mitochondrial activity and homeostasis. As mitochondria biogenesis is controlled by the nucleus and almost all mitochondrial proteins are encoded by nuclear genes, a tight communication network between mitochondria and the nucleus has evolved, which includes signaling cascades, proteins which are dual-localized to the two compartments, and sensing of mitochondrial products by nuclear proteins. All of these enable a crosstalk between mitochondria and the nucleus that allows the 'ground control' to get information on mitochondria's status. Such information facilitates the creation of a cellular balance of mitochondrial status with energetic needs. This communication also allows a transcriptional response in case mitochondrial function is impaired aimed to restore mitochondrial homeostasis. As mitochondrial dysfunction is related to a growing number of genetic diseases as well as neurodegenerative conditions and aging, elucidating the mechanisms governing the mitochondrial/nuclear communication should progress a better understanding of mitochondrial dysfunctions.

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Cytosolic Hsp60 Can Modulate Proteasome Activity in Yeast

Cited by 29 publications

References 43 publications

Functional Compartmentalization of HSP60-Survivin Interaction between Mitochondria and Cytosol in Cancer Cells

Functional Compartmentalization of HSP60-Survivin Interaction between Mitochondria and Cytosol in Cancer Cells

Heat shock protein 60 (HSP60) modulates adiponectin signaling by stabilizing adiponectin receptor

Ground control to major TOM: mitochondria–nucleus communication

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