Mitochondrial proton and electron leaks.
Mitochondrial proton and electron leaks.
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DOI：
10.1042/bse0470053
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发表时间：
2010
影响因子：
6.4
通讯作者：
Brand MD
中科院分区：
文献类型：
--
作者：
Jastroch M;Divakaruni AS;Mookerjee S;Treberg JR;Brand MD
线粒体质子和电子泄漏对线粒体偶联效率和活性氧的产生有重要影响。在本章的第一部分，我们讨论了基础和诱导质子泄漏途径的分子性质，以及它们的生理重要性。基底泄漏是不受调节的，大部分可归因于线粒体阴离子载体，而通过脂质双分子层的质子泄漏似乎较少。基底质子泄漏是细胞类型特异性的，与代谢率相关。通过腺嘌呤核苷酸转位酶（ANT）和解偶联蛋白（UCPs）诱导的泄漏可以被脂肪酸、超氧化物或过氧化产物激活。通过UCP1诱导渗漏在哺乳动物棕色脂肪组织中的生理作用是产热，而非哺乳动物UCP1及其旁系蛋白，特别是UCP2和UCP3的作用尚不清楚。本章的第二部分着重于发生在线粒体电子传递链中的电子泄漏。在细胞色素c氧化酶将氧还原为水之前，电子的出口导致超氧化物的产生。由于电子泄漏的机制对理解其生理相关性至关重要，我们总结了分离线粒体中复合体I和III的电子泄漏机制和拓扑结构。我们还强调了评估活细胞中电子泄漏的最新进展和挑战。最后，我们强调质子和电子泄漏作为体重调节和胰岛素分泌的治疗靶点的重要性。
Mitochondrial proton and electron leak have a major impact on mitochondrial coupling efficiency and production of reactive oxygen species. In the first part of this chapter, we address the molecular nature of the basal and inducible proton leak pathways, and their physiological importance. The basal leak is unregulated, and a major proportion can be attributed to mitochondrial anion carriers, while the proton leak through the lipid bilayer appears to be minor. The basal proton leak is cell-type specific and correlates with metabolic rate. The inducible leak through the adenine nucleotide translocase (ANT) and uncoupling proteins (UCPs) can be activated by fatty acids, superoxide, or peroxidation products. The physiological role of inducible leak through UCP1 in mammalian brown adipose tissue is heat production, whereas the roles of non-mammalian UCP1 and its paralogous proteins, in particular UCP2 and UCP3, are not yet resolved. The second part of the chapter focuses on the electron leak that occurs in the mitochondrial electron transport chain. Exit of electrons prior to the reduction of oxygen to water at cytochrome c oxidase causes the production of superoxide. As the mechanisms of electron leak are crucial to understanding their physiological relevance, we summarize the mechanisms and topology of electron leak from Complex I and III in studies using isolated mitochondria. We also highlight recent progress and challenges of assessing electron leak in the living cell. Finally, we emphasise the importance of proton and electron leak as therapeutic targets in body weight regulation and insulin secretion.
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影响因子：
11.4
作者：
KLINGENBERG, M;WINKLER, E
通讯作者：
WINKLER, E
DOI：
10.1046/j.1467-789x.2001.00043.x
发表时间：
2001-11-01
期刊：
Obesity reviews : an official journal of the International Association for the Study of Obesity
影响因子：
--
作者：
Harper, J A;Dickinson, K;Brand, M D
通讯作者：
Brand, M D
DOI：
10.1073/pnas.0510977103
发表时间：
2006-05-16
影响因子：
11.1
作者：
Kussmaul, Lothar;Hirst, Judy
通讯作者：
Hirst, Judy
影响因子：
4.6
作者：
Jastroch, M.;Withers, K. W.;Klingenspor, M.
通讯作者：
Klingenspor, M.
影响因子：
4.1
作者：
Brand, MD;Pakay, JL;Cornwall, EJ
通讯作者：
Cornwall, EJ