Tossounian Maria-Armineh, Zhang Bruce, Gout Ivan
Department of Structural and Molecular Biology, University College London, London WC1E 6BT, UK.
Antioxidants (Basel). 2020 Dec 16;9(12):1288. doi: 10.3390/antiox9121288.
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, -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.
3-磷酸甘油醛脱氢酶（GAPDH）是一种关键的糖酵解酶，对葡萄糖分解以提供细胞能量至关重要。在过去十年中，GAPDH被报道为翻译后修饰（PTM）最显著的细胞靶点之一，这些修饰使GAPDH转向不同的非糖酵解功能。因此，它被称为兼职蛋白。在代谢和氧化应激期间，GAPDH是不同氧化翻译后修饰（oxPTM）的靶点，例如亚磺酰化、硫醇化、亚硝基化和硫氢化。这些修饰改变了酶的构象、亚细胞定位以及与下游伙伴的调节相互作用，从而影响其糖酵解和非糖酵解功能。在这篇综述中，我们讨论了不同氧化还原书写者对GAPDH的氧化还原调节，这些书写者在GAPDH上引入oxPTM密码以指导氧化还原反应；GAPDH阅读者，它们通过调节相互作用解读oxPTM密码并通过形成多酶信号复合物协调细胞反应；以及氧化还原擦除者，它们是使GAPDH催化活性再生的还原系统。还讨论了与氧化诱导的GAPDH失调相关的人类病理学，突出了GAPDH氧化还原调节在神经退行性变和代谢紊乱中的重要性。
