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线粒体生理学与S-(去)亚硝基化相互作用的既定原则与新兴概念:对癌症和神经退行性疾病的影响

Established Principles and Emerging Concepts on the Interplay between Mitochondrial Physiology and S-(De)nitrosylation: Implications in Cancer and Neurodegeneration.

作者信息

Di Giacomo Giuseppina, Rizza Salvatore, Montagna Costanza, Filomeni Giuseppe

机构信息

Research Centre IRCCS San Raffaele Pisana, Via di Val Cannuta, 247, 00166 Rome, Italy.

出版信息

Int J Cell Biol. 2012;2012:361872. doi: 10.1155/2012/361872. Epub 2012 Aug 13.

Abstract

S-nitrosylation is a posttranslational modification of cysteine residues that has been frequently indicated as potential molecular mechanism governing cell response upon redox unbalance downstream of nitric oxide (over)production. In the last years, increased levels of S-nitrosothiols (SNOs) have been tightly associated with the onset of nitroxidative stress-based pathologies (e.g., cancer and neurodegeneration), conditions in which alterations of mitochondrial homeostasis and activation of cellular processes dependent on it have been reported as well. In this paper we aim at summarizing the current knowledge of mitochondria-related proteins undergoing S-nitrosylation and how this redox modification might impact on mitochondrial functions, whose impairment has been correlated to tumorigenesis and neuronal cell death. In particular, emphasis will be given to the possible, but still neglected implication of denitrosylation reactions in the modulation of mitochondrial SNOs and how they can affect mitochondrion-related cellular process, such as oxidative phosphorylation, mitochondrial dynamics, and mitophagy.

摘要

S-亚硝基化是半胱氨酸残基的一种翻译后修饰,常被认为是在一氧化氮(过度)产生下游的氧化还原失衡时调控细胞反应的潜在分子机制。在过去几年中,S-亚硝基硫醇(SNOs)水平的升高与基于氮氧化应激的疾病(如癌症和神经退行性变)的发生密切相关,在这些疾病中也报道了线粒体稳态的改变以及依赖于它的细胞过程的激活。在本文中,我们旨在总结目前关于发生S-亚硝基化的线粒体相关蛋白的知识,以及这种氧化还原修饰如何影响线粒体功能,而线粒体功能的损害与肿瘤发生和神经元细胞死亡相关。特别地,将重点讨论去亚硝基化反应在调节线粒体SNOs方面可能但仍被忽视的影响,以及它们如何影响与线粒体相关的细胞过程,如氧化磷酸化、线粒体动力学和线粒体自噬。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/768a/3425078/2fd9780b2130/IJCB2012-361872.001.jpg

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