scholarly journals Link between Heat Shock Protein 90 and the Mitochondrial Respiratory Chain in the Caspofungin Stress Response of Aspergillus fumigatus

2019 ◽  
Vol 63 (7) ◽  
Author(s):  
M. Aruanno ◽  
D. Bachmann ◽  
D. Sanglard ◽  
F. Lamoth
Keyword(s):  
Stress Response ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Complex I ◽  
Heat Shock Protein 90 ◽  
Mitochondrial Respiratory Chain ◽  
Paradoxical Effect ◽  
Line Treatment ◽  
Content Type

ABSTRACT Aspergillus fumigatus is an opportunistic mold responsible for invasive aspergillosis. Triazoles (e.g., voriconazole) represent the first-line treatment, but emerging resistance is of concern. The echinocandin drug caspofungin is used as second-line treatment but has limited efficacy. The heat shock protein 90 (Hsp90) orchestrates the caspofungin stress response and is the trigger of an adaptive phenomenon called the paradoxical effect (growth recovery at increasing caspofungin concentrations). The aim of this study was to elucidate the Hsp90-dependent mechanisms of the caspofungin stress response. Transcriptomic profiles of the wild-type A. fumigatus strain (KU80) were compared to those of a mutant strain with substitution of the native hsp90 promoter by the thiA promoter (pthiA-hsp90), which lacks the caspofungin paradoxical effect. Caspofungin induced expression of the genes of the mitochondrial respiratory chain (MRC), in particular, NADH-ubiquinone oxidoreductases (complex I), in KU80 but not in the pthiA-hsp90 mutant. The caspofungin paradoxical effect could be abolished by rotenone (MRC complex I inhibitor) in KU80, supporting the role of MRC in the caspofungin stress response. Fluorescent staining of active mitochondria and measurement of oxygen consumption and ATP production confirmed the activation of the MRC in KU80 in response to caspofungin, but this activity was impaired in the pthiA-hsp90 mutant. Using a bioluminescent reporter for the measurement of intracellular calcium, we demonstrated that inhibition of Hsp90 by geldanamycin or MRC complex I by rotenone prevented the increase in intracellular calcium shown to be essential for the caspofungin paradoxical effect. In conclusion, our data support a role of the MRC in the caspofungin stress response which is dependent on Hsp90.

scholarly journals Heat Shock Protein 90 as Therapeutic Target for CVDs and Heart Ageing

2022 ◽  
Vol 23 (2) ◽  
pp. 649
Author(s):  
Siarhei A. Dabravolski ◽  
Vasily N. Sukhorukov ◽  
Vladislav A. Kalmykov ◽  
Nikolay A. Orekhov ◽  
Andrey V. Grechko ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Molecular Chaperones ◽  
Heat Shock Protein 90 ◽  
Misfolded Proteins ◽  
Heart Cells ◽  
Metabolic Demand ◽  
Heart Protection ◽  
High Metabolic Demand

Cardiovascular diseases (CVDs) are the leading cause of death globally, representing approximately 32% of all deaths worldwide. Molecular chaperones are involved in heart protection against stresses and age-mediated accumulation of toxic misfolded proteins by regulation of the protein synthesis/degradation balance and refolding of misfolded proteins, thus supporting the high metabolic demand of the heart cells. Heat shock protein 90 (HSP90) is one of the main cardioprotective chaperones, represented by cytosolic HSP90a and HSP90b, mitochondrial TRAP1 and ER-localised Grp94 isoforms. Currently, the main way to study the functional role of HSPs is the application of HSP inhibitors, which could have a different way of action. In this review, we discussed the recently investigated role of HSP90 proteins in cardioprotection, atherosclerosis, CVDs development and the involvements of HSP90 clients in the activation of different molecular pathways and signalling mechanisms, related to heart ageing.

Role of heat shock protein 90 in bradykinin-stimulated endothelial nitric oxide release

2000 ◽  
Vol 35 (3) ◽  
pp. 165-170 ◽  
Author(s):  
M.Brennan Harris ◽  
Hong Ju ◽  
Virginia J. Venema ◽  
Michele Blackstone ◽  
Richard C. Venema
Keyword(s):  
Nitric Oxide ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Nitric Oxide Release ◽  
Endothelial Nitric Oxide

scholarly journals Mechanisms of Disease: the role of heat-shock protein 90 in genitourinary malignancy

2006 ◽  
Vol 3 (11) ◽  
pp. 590-601 ◽  
Author(s):  
Jean-Baptiste Lattouf ◽  
Ramaprasad Srinivasan ◽  
Peter A Pinto ◽  
W Marston Linehan ◽  
Leonard Neckers
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90

scholarly journals Adaptation of the Wine Bacterium Oenococcus oeni to Ethanol Stress: Role of the Small Heat Shock Protein Lo18 in Membrane Integrity

2014 ◽  
Vol 80 (10) ◽  
pp. 2973-2980 ◽  
Author(s):  
Magali Maitre ◽  
Stéphanie Weidmann ◽  
Florence Dubois-Brissonnet ◽  
Vanessa David ◽  
Jacques Covès ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Phospholipid Composition ◽  
Small Heat Shock Protein ◽  
Oenococcus Oeni ◽  
Lipid Binding ◽  
Phospholipid Content ◽  
Ethanol Stress ◽  
Content Type

ABSTRACTMalolactic fermentation in wine is often carried out byOenococcus oeni. Wine is a stressful environment for bacteria because ethanol is a toxic compound that impairs the integrity of bacterial membranes. The small heat shock protein (sHsp) Lo18 is an essential actor of the stress response inO. oeni. Lo18 prevents the thermal aggregation of proteins and plays a crucial role in membrane quality control. Here, we investigated the interaction between Lo18 and four types of liposomes: one was prepared fromO. oenigrown under optimal growth conditions (here, control liposomes), one was prepared fromO. oenigrown in the presence of 8% ethanol (here, ethanol liposomes), one was prepared from synthetic phospholipids, and one was prepared from phospholipids fromBacillus subtilisorLactococcus lactis. We observed the strongest interaction between Lo18 and control liposomes. The lipid binding activity of Lo18 required the dissociation of oligomeric structures into dimers. Protein protection experiments carried out in the presence of the liposomes fromO. oenisuggested that Lo18 had a higher affinity for control liposomes than for a model protein. In anisotropy experiments, we mimicked ethanol action by temperature-dependent fluidization of the liposomes. Results suggest that the principal determinant of Lo18-membrane interaction is lipid bilayer phase behavior rather than phospholipid composition. We suggest a model to describe the ethanol adaptation ofO. oeni. This model highlights the dual role of Lo18 in the protection of proteins from aggregation and membrane stabilization and suggests how modifications of phospholipid content may be a key factor determining the balance between these two functions.

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