Hsp60 Post-translational Modifications: Functional and Pathological Consequences
Hsp60 is a chaperone belonging to the Chaperonins of Group I and typically functions inside mitochondria in which, together with the co-chaperonin Hsp10, maintains protein homeostasis. In addition to this canonical role, Hsp60 plays many others beyond the mitochondria, for instance in the cytosol, p...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmolb.2020.00095/full |
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| author | Celeste Caruso Bavisotto Celeste Caruso Bavisotto Giusi Alberti Alessandra Maria Vitale Letizia Paladino Claudia Campanella Francesca Rappa Magdalena Gorska Everly Conway de Macario Everly Conway de Macario Francesco Cappello Francesco Cappello Alberto J. L. Macario Alberto J. L. Macario Antonella Marino Gammazza |
| author_facet | Celeste Caruso Bavisotto Celeste Caruso Bavisotto Giusi Alberti Alessandra Maria Vitale Letizia Paladino Claudia Campanella Francesca Rappa Magdalena Gorska Everly Conway de Macario Everly Conway de Macario Francesco Cappello Francesco Cappello Alberto J. L. Macario Alberto J. L. Macario Antonella Marino Gammazza |
| author_sort | Celeste Caruso Bavisotto |
| collection | DOAJ |
| description | Hsp60 is a chaperone belonging to the Chaperonins of Group I and typically functions inside mitochondria in which, together with the co-chaperonin Hsp10, maintains protein homeostasis. In addition to this canonical role, Hsp60 plays many others beyond the mitochondria, for instance in the cytosol, plasma-cell membrane, extracellular space, and body fluids. These non-canonical functions include participation in inflammation, autoimmunity, carcinogenesis, cell replication, and other cellular events in health and disease. Thus, Hsp60 is a multifaceted molecule with a wide range of cellular and tissue locations and functions, which is noteworthy because there is only one hsp60 gene. The question is by what mechanism this protein can become multifaceted. Likely, one factor contributing to this diversity is post-translational modification (PTM). The amino acid sequence of Hsp60 contains many potential phosphorylation sites, and other PTMs are possible such as O-GlcNAcylation, nitration, acetylation, S-nitrosylation, citrullination, oxidation, and ubiquitination. The effect of some of these PTMs on Hsp60 functions have been examined, for instance phosphorylation has been implicated in sperm capacitation, docking of H2B and microtubule-associated proteins, mitochondrial dysfunction, tumor invasiveness, and delay or facilitation of apoptosis. Nitration was found to affect the stability of the mitochondrial permeability transition pore, to inhibit folding ability, and to perturb insulin secretion. Hyperacetylation was associated with mitochondrial failure; S-nitrosylation has an impact on mitochondrial stability and endothelial integrity; citrullination can be pro-apoptotic; oxidation has a role in the response to cellular injury and in cell migration; and ubiquitination regulates interaction with the ubiquitin-proteasome system. Future research ought to determine which PTM causes which variations in the Hsp60 molecular properties and functions, and which of them are pathogenic, causing chaperonopathies. This is an important topic considering the number of acquired Hsp60 chaperonopathies already cataloged, many of which are serious diseases without efficacious treatment. |
| first_indexed | 2024-04-12T04:30:10Z |
| format | Article |
| id | doaj.art-7b18940fb14045588dc1044f613ead13 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-12T04:30:10Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-7b18940fb14045588dc1044f613ead132022-12-22T03:47:57ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2020-06-01710.3389/fmolb.2020.00095527150Hsp60 Post-translational Modifications: Functional and Pathological ConsequencesCeleste Caruso Bavisotto0Celeste Caruso Bavisotto1Giusi Alberti2Alessandra Maria Vitale3Letizia Paladino4Claudia Campanella5Francesca Rappa6Magdalena Gorska7Everly Conway de Macario8Everly Conway de Macario9Francesco Cappello10Francesco Cappello11Alberto J. L. Macario12Alberto J. L. Macario13Antonella Marino Gammazza14Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostic (BIND), University of Palermo, Palermo, ItalyEuro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, ItalySection of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostic (BIND), University of Palermo, Palermo, ItalySection of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostic (BIND), University of Palermo, Palermo, ItalySection of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostic (BIND), University of Palermo, Palermo, ItalySection of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostic (BIND), University of Palermo, Palermo, ItalySection of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostic (BIND), University of Palermo, Palermo, ItalyDepartment of Medical Chemistry, Medical University of Gdańsk, Gdańsk, PolandEuro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, ItalyDepartment of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore-Institute of Marine and Environmental Technology (IMET), Baltimore, MD, United StatesSection of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostic (BIND), University of Palermo, Palermo, ItalyEuro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, ItalyEuro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, ItalyDepartment of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore-Institute of Marine and Environmental Technology (IMET), Baltimore, MD, United StatesSection of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostic (BIND), University of Palermo, Palermo, ItalyHsp60 is a chaperone belonging to the Chaperonins of Group I and typically functions inside mitochondria in which, together with the co-chaperonin Hsp10, maintains protein homeostasis. In addition to this canonical role, Hsp60 plays many others beyond the mitochondria, for instance in the cytosol, plasma-cell membrane, extracellular space, and body fluids. These non-canonical functions include participation in inflammation, autoimmunity, carcinogenesis, cell replication, and other cellular events in health and disease. Thus, Hsp60 is a multifaceted molecule with a wide range of cellular and tissue locations and functions, which is noteworthy because there is only one hsp60 gene. The question is by what mechanism this protein can become multifaceted. Likely, one factor contributing to this diversity is post-translational modification (PTM). The amino acid sequence of Hsp60 contains many potential phosphorylation sites, and other PTMs are possible such as O-GlcNAcylation, nitration, acetylation, S-nitrosylation, citrullination, oxidation, and ubiquitination. The effect of some of these PTMs on Hsp60 functions have been examined, for instance phosphorylation has been implicated in sperm capacitation, docking of H2B and microtubule-associated proteins, mitochondrial dysfunction, tumor invasiveness, and delay or facilitation of apoptosis. Nitration was found to affect the stability of the mitochondrial permeability transition pore, to inhibit folding ability, and to perturb insulin secretion. Hyperacetylation was associated with mitochondrial failure; S-nitrosylation has an impact on mitochondrial stability and endothelial integrity; citrullination can be pro-apoptotic; oxidation has a role in the response to cellular injury and in cell migration; and ubiquitination regulates interaction with the ubiquitin-proteasome system. Future research ought to determine which PTM causes which variations in the Hsp60 molecular properties and functions, and which of them are pathogenic, causing chaperonopathies. This is an important topic considering the number of acquired Hsp60 chaperonopathies already cataloged, many of which are serious diseases without efficacious treatment.https://www.frontiersin.org/article/10.3389/fmolb.2020.00095/fullHsp60chaperonincanonical functionsnon-canonical functionspost-translation modificationchaperonopathies |
| spellingShingle | Celeste Caruso Bavisotto Celeste Caruso Bavisotto Giusi Alberti Alessandra Maria Vitale Letizia Paladino Claudia Campanella Francesca Rappa Magdalena Gorska Everly Conway de Macario Everly Conway de Macario Francesco Cappello Francesco Cappello Alberto J. L. Macario Alberto J. L. Macario Antonella Marino Gammazza Hsp60 Post-translational Modifications: Functional and Pathological Consequences Frontiers in Molecular Biosciences Hsp60 chaperonin canonical functions non-canonical functions post-translation modification chaperonopathies |
| title | Hsp60 Post-translational Modifications: Functional and Pathological Consequences |
| title_full | Hsp60 Post-translational Modifications: Functional and Pathological Consequences |
| title_fullStr | Hsp60 Post-translational Modifications: Functional and Pathological Consequences |
| title_full_unstemmed | Hsp60 Post-translational Modifications: Functional and Pathological Consequences |
| title_short | Hsp60 Post-translational Modifications: Functional and Pathological Consequences |
| title_sort | hsp60 post translational modifications functional and pathological consequences |
| topic | Hsp60 chaperonin canonical functions non-canonical functions post-translation modification chaperonopathies |
| url | https://www.frontiersin.org/article/10.3389/fmolb.2020.00095/full |
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