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The Writers, Readers, and Erasers in Redox Regulation of GAPDH

Glyceraldehyde 3–phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme, which is crucial for the breakdown of glucose to provide cellular energy. Over the past decade, GAPDH has been reported to be one of the most prominent cellular targets of post-translational modifications (PTMs), which dive...

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Autores principales: Tossounian, Maria-Armineh, Zhang, Bruce, Gout, Ivan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765867/
https://www.ncbi.nlm.nih.gov/pubmed/33339386
http://dx.doi.org/10.3390/antiox9121288
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author Tossounian, Maria-Armineh
Zhang, Bruce
Gout, Ivan
author_facet Tossounian, Maria-Armineh
Zhang, Bruce
Gout, Ivan
author_sort Tossounian, Maria-Armineh
collection PubMed
description Glyceraldehyde 3–phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme, which is crucial for the breakdown of glucose to provide cellular energy. Over the past decade, GAPDH has been reported to be one of the most prominent cellular targets of post-translational modifications (PTMs), which divert GAPDH toward different non-glycolytic functions. Hence, it is termed a moonlighting protein. During metabolic and oxidative stress, GAPDH is a target of different oxidative PTMs (oxPTM), e.g., sulfenylation, S-thiolation, nitrosylation, and sulfhydration. These modifications alter the enzyme’s conformation, subcellular localization, and regulatory interactions with downstream partners, which impact its glycolytic and non-glycolytic functions. In this review, we discuss the redox regulation of GAPDH by different redox writers, which introduce the oxPTM code on GAPDH to instruct a redox response; the GAPDH readers, which decipher the oxPTM code through regulatory interactions and coordinate cellular response via the formation of multi-enzyme signaling complexes; and the redox erasers, which are the reducing systems that regenerate the GAPDH catalytic activity. Human pathologies associated with the oxidation-induced dysregulation of GAPDH are also discussed, featuring the importance of the redox regulation of GAPDH in neurodegeneration and metabolic disorders.
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spelling pubmed-77658672020-12-28 The Writers, Readers, and Erasers in Redox Regulation of GAPDH Tossounian, Maria-Armineh Zhang, Bruce Gout, Ivan Antioxidants (Basel) Review Glyceraldehyde 3–phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme, which is crucial for the breakdown of glucose to provide cellular energy. Over the past decade, GAPDH has been reported to be one of the most prominent cellular targets of post-translational modifications (PTMs), which divert GAPDH toward different non-glycolytic functions. Hence, it is termed a moonlighting protein. During metabolic and oxidative stress, GAPDH is a target of different oxidative PTMs (oxPTM), e.g., sulfenylation, S-thiolation, nitrosylation, and sulfhydration. These modifications alter the enzyme’s conformation, subcellular localization, and regulatory interactions with downstream partners, which impact its glycolytic and non-glycolytic functions. In this review, we discuss the redox regulation of GAPDH by different redox writers, which introduce the oxPTM code on GAPDH to instruct a redox response; the GAPDH readers, which decipher the oxPTM code through regulatory interactions and coordinate cellular response via the formation of multi-enzyme signaling complexes; and the redox erasers, which are the reducing systems that regenerate the GAPDH catalytic activity. Human pathologies associated with the oxidation-induced dysregulation of GAPDH are also discussed, featuring the importance of the redox regulation of GAPDH in neurodegeneration and metabolic disorders. MDPI 2020-12-16 /pmc/articles/PMC7765867/ /pubmed/33339386 http://dx.doi.org/10.3390/antiox9121288 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Tossounian, Maria-Armineh
Zhang, Bruce
Gout, Ivan
The Writers, Readers, and Erasers in Redox Regulation of GAPDH
title The Writers, Readers, and Erasers in Redox Regulation of GAPDH
title_full The Writers, Readers, and Erasers in Redox Regulation of GAPDH
title_fullStr The Writers, Readers, and Erasers in Redox Regulation of GAPDH
title_full_unstemmed The Writers, Readers, and Erasers in Redox Regulation of GAPDH
title_short The Writers, Readers, and Erasers in Redox Regulation of GAPDH
title_sort writers, readers, and erasers in redox regulation of gapdh
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765867/
https://www.ncbi.nlm.nih.gov/pubmed/33339386
http://dx.doi.org/10.3390/antiox9121288
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