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线粒体氧化还原信号研究的陷阱

Pitfalls of Mitochondrial Redox Signaling Research.

作者信息

Ježek Petr

机构信息

Department of Mitochondrial Physiology, No. 75, Institute of Physiology of the Czech Academy of Sciences, Vídeňská 1083, 14220 Prague, Czech Republic.

出版信息

Antioxidants (Basel). 2023 Aug 31;12(9):1696. doi: 10.3390/antiox12091696.

DOI:10.3390/antiox12091696
PMID:37759999
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10525995/
Abstract

Redox signaling from mitochondria (mt) to the cytosol and plasma membrane (PM) has been scarcely reported, such as in the case of hypoxic cell adaptation or (2-oxo-) 2-keto-isocaproate (KIC) β-like-oxidation stimulating insulin secretion in pancreatic β-cells. Mutual redox state influence between mitochondrial major compartments, the matrix and the intracristal space, and the cytosol is therefore derived theoretically in this article to predict possible conditions, when mt-to-cytosol and mt-to-PM signals may occur, as well as conditions in which the cytosolic redox signaling is not overwhelmed by the mitochondrial antioxidant capacity. Possible peroxiredoxin 3 participation in mt-to-cytosol redox signaling is discussed, as well as another specific case, whereby mitochondrial superoxide release is diminished, whereas the matrix MnSOD is activated. As a result, the enhanced conversion to HO allows HO diffusion into the cytosol, where it could be a predominant component of the HO release. In both of these ways, mt-to-cytosol and mt-to-PM signals may be realized. Finally, the use of redox-sensitive probes is discussed, which disturb redox equilibria, and hence add a surplus redox-buffering to the compartment, where they are localized. Specifically, when attempts to quantify net HO fluxes are to be made, this should be taken into account.

摘要

线粒体(mt)向细胞质和质膜(PM)的氧化还原信号传导鲜有报道,比如在缺氧细胞适应的情况下,或者(2-氧代-)2-酮异己酸(KIC)β-氧化刺激胰腺β细胞分泌胰岛素的情况。因此,本文从理论上推导了线粒体主要区室(基质和嵴内空间)与细胞质之间相互的氧化还原状态影响,以预测可能出现线粒体到细胞质以及线粒体到质膜信号的条件,以及细胞质氧化还原信号不会被线粒体抗氧化能力淹没的条件。文中讨论了过氧化物还原酶3可能参与线粒体到细胞质的氧化还原信号传导,以及另一种特殊情况,即线粒体超氧化物释放减少,而基质锰超氧化物歧化酶被激活。结果,向过氧化氢的转化增强,使得过氧化氢扩散到细胞质中,在那里它可能是过氧化氢释放的主要成分。通过这两种方式,线粒体到细胞质以及线粒体到质膜的信号可能得以实现。最后,讨论了氧化还原敏感探针的使用,这些探针会干扰氧化还原平衡,从而在其所在的区室中增加额外的氧化还原缓冲。具体而言,当试图量化净过氧化氢通量时,应该考虑到这一点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/015c/10525995/6687875e5e0f/antioxidants-12-01696-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/015c/10525995/e0c30537fef1/antioxidants-12-01696-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/015c/10525995/8adf36eefea6/antioxidants-12-01696-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/015c/10525995/bc896ac6895e/antioxidants-12-01696-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/015c/10525995/6687875e5e0f/antioxidants-12-01696-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/015c/10525995/e0c30537fef1/antioxidants-12-01696-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/015c/10525995/8adf36eefea6/antioxidants-12-01696-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/015c/10525995/bc896ac6895e/antioxidants-12-01696-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/015c/10525995/6687875e5e0f/antioxidants-12-01696-g004.jpg

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