Jastroch 2010 Essays Biochemistry

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Jastroch M, Divakaruni AS, MookerjeecS, Treberg JR, Brand MD (2010) Mitochondrial proton and electron leaks. Essays Biochem 47: 53–67.

Β» PMDI:3122475 Open Access

Jastroch M, Divakaruni AS, MookerjeecS, Treberg JR, Brand MD (2010) Essays Biochem

Abstract: 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. β€’ Keywords: Proton leak, electron leak, uncoupling, reactive oxygen species, superoxide, basal proton leak, adenine nucleotide translocase, uncoupling protein, ucp, superoxide, brown adipose tissue, mitochondrial anion carriers, insulin secretion, obesity, aging, semiquinone radical, DNP, GSIS, beta cells β€’ Bioblast editor: Iglesias-Gonzalez J

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