Mitochondrial Lon protease in human disease and aging: Including an etiologic classification of Lon-related diseases and disorders.
Mitochondrial Lon protease in human disease and aging: Including an etiologic classification of Lon-related diseases and disorders.
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DOI：
10.1016/j.freeradbiomed.2016.06.031
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发表时间：
2016-11
影响因子：
7.4
通讯作者：
Davies, Kelvin J. A.
中科院分区：
文献类型：
--
作者：
Bota, Daniela A.;Davies, Kelvin J. A.
关键词：
线粒体Lon蛋白酶，也称为LonP 1，是核基因LONP 1的产物。Lon是线粒体代谢和响应自由基损伤的主要调节剂，也是线粒体DNA维持和修复的重要因子。Lon是一种ATP刺激的蛋白酶，其在与线粒体基因组结合（在线粒体内膜的内表面）和释放到线粒体基质中之间循环，在线粒体基质中其可以降解基质蛋白。Lon至少有三种不同的作用或功能：1）氧化蛋白的蛋白水解消化和特定必需线粒体酶如乌头酸酶、TFAM和星星的周转; 2）线粒体（mt）DNA结合蛋白，参与mtDNA复制和有丝分裂; 3）蛋白伴侣，与Hsp 60-mtHsp 70复合物相互作用。LONP 1的直系同源基因已经在细菌、酵母、苍蝇、蠕虫和哺乳动物中进行了研究，表明该基因的广泛重要性以及其显着的进化保守性。近年来，我们已经见证了关于Lon参与生理功能的知识的显着增加，以及不断扩大的人类疾病，包括癌症，神经退行性疾病，心脏病和中风。此外，Lon似乎在衰老过程中起着重要作用。现在已经确定了许多线粒体疾病，其机制涉及不同程度的Lon功能障碍。在本文中，我们回顾了正常条件下Lon功能的现有知识，并提出了一种新的人类疾病分类，其特征是Lon过度表达或功能下降或丧失。Lon也与人类衰老有关，我们回顾了目前可用的数据，并推测衰老和疾病可能的相互作用。最后，我们还讨论了Lon作为人类疾病潜在的治疗靶点。
The Mitochondrial Lon protease, also called LonP1 is a product of the nuclear gene LONP1. Lon is a major regulator of mitochondrial metabolism and response to free radical damage, as well as an essential factor for the maintenance and repair of mitochondrial DNA. Lon is an ATP-stimulated protease that cycles between being bound (at the inner surface of the inner mitochondrial membrane) to the mitochondrial genome, and being released into the mitochondrial matrix where it can degrade matrix proteins. At least three different roles or functions have been ascribed to Lon: 1) Proteolytic digestion of oxidized proteins and the turnover of specific essential mitochondrial enzymes such as aconitase, TFAM, and StAR; 2) Mitochondrial (mt)DNA-binding protein, involved in mtDNA replication and mitogenesis; and 3) Protein chaperone, interacting with the Hsp60–mtHsp70 complex. LONP1 orthologs have been studied in bacteria, yeast, flies, worms, and mammals, evincing the widespread importance of the gene, as well as its remarkable evolutionary conservation. In recent years, we have witnessed a significant increase in knowledge regarding Lon's involvement in physiological functions, as well as in an expanding array of human disorders, including cancer, neurodegeneration, heart disease, and stroke. In addition, Lon appears to have a significant role in the aging process. A number of mitochondrial diseases have now been identified whose mechanisms involve various degrees of Lon dysfunction. In this paper we review current knowledge of Lon's function, under normal conditions, and we propose a new classification of human diseases characterized by a either over-expression or decline or loss of function of Lon. Lon has also been implicated in human aging, and we review the data currently available as well as speculating about possible interactions of aging and disease. Finally, we also discuss Lon as potential therapeutic target in human disease.
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DOI：
10.1042/bj20091321
发表时间：
2010-01-27
期刊：
The Biochemical journal
影响因子：
--
作者：
Azzu V;Mookerjee SA;Brand MD
通讯作者：
Brand MD
影响因子：
3.5
作者：
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通讯作者：
GORBALENYA, AE
影响因子：
9
作者：
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DOI：
10.1046/j.1432-1033.2003.03598.x
发表时间：
2003-05-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Bakala, H;Delaval, E;Friguet, B
通讯作者：
Friguet, B
影响因子：
3.9
作者：
Bayot, Aurelien;Gareil, Monique;Bulteau, Anne-Laure
通讯作者：
Bulteau, Anne-Laure