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J Mol Biol. 2018 Oct 19;430(21):3873-3891. doi: 10.1016/j.jmb.2018.03.025. Epub 2018 Apr 4.

Use the Protonmotive Force: Mitochondrial Uncoupling and Reactive Oxygen Species.

Author information

1
Department of Pharmacology and Physiology, University of Rochester Medical Center, Box 711/604, 575 Elmwood Ave., Rochester, NY 14642, USA. Electronic address: brandon_berry@urmc.rochester.edu.
2
Department of Anesthesiology and Perioperative Medicine, University of Rochester Medical Center, Box 711/604, 575 Elmwood Ave., Rochester, NY 14642, USA. Electronic address: adam_trewin@urmc.rochester.edu.
3
Department of Pathology, University of Rochester Medical Center, Box 609, 601 Elmwood Ave., Rochester, NY 14642, USA; Department of Microbiology and Immunology, University of Rochester Medical Center, Box 609, 601 Elmwood Ave., Rochester, NY 14642, USA. Electronic address: andrea_amitrano@urmc.rochester.edu.
4
Department of Pharmacology and Physiology, University of Rochester Medical Center, Box 711/604, 575 Elmwood Ave., Rochester, NY 14642, USA; Department of Pathology, University of Rochester Medical Center, Box 609, 601 Elmwood Ave., Rochester, NY 14642, USA; Department of Microbiology and Immunology, University of Rochester Medical Center, Box 609, 601 Elmwood Ave., Rochester, NY 14642, USA. Electronic address: minsoo_kim@rurmc.rochester.edu.
5
Department of Pharmacology and Physiology, University of Rochester Medical Center, Box 711/604, 575 Elmwood Ave., Rochester, NY 14642, USA; Department of Anesthesiology and Perioperative Medicine, University of Rochester Medical Center, Box 711/604, 575 Elmwood Ave., Rochester, NY 14642, USA. Electronic address: andrew_wojtovich@urmc.rochester.edu.

Abstract

Mitochondrial respiration results in an electrochemical proton gradient, or protonmotive force (pmf), across the mitochondrial inner membrane. The pmf is a form of potential energy consisting of charge (∆ψm) and chemical (∆pH) components, that together drive ATP production. In a process called uncoupling, proton leak into the mitochondrial matrix independent of ATP production dissipates the pmf and energy is lost as heat. Other events can directly dissipate the pmf independent of ATP production as well, such as chemical exposure or mechanisms involving regulated mitochondrial membrane electrolyte transport. Uncoupling has defined roles in metabolic plasticity and can be linked through signal transduction to physiologic events. In the latter case, the pmf impacts mitochondrial reactive oxygen species (ROS) production. Although capable of molecular damage, ROS also have signaling properties that depend on the timing, location, and quantity of their production. In this review, we provide a general overview of mitochondrial ROS production, mechanisms of uncoupling, and how these work in tandem to affect physiology and pathologies, including obesity, cardiovascular disease, and immunity. Overall, we highlight that isolated bioenergetic models-mitochondria and cells-only partially recapitulate the complex link between the pmf and ROS signaling that occurs in vivo.

KEYWORDS:

T cells; brown adipose tissue; ischemia–reperfusion injury; mitochondria; proton leak

PMID:
29626541
PMCID:
PMC6170739
[Available on 2019-10-19]
DOI:
10.1016/j.jmb.2018.03.025

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