Mitochondrial metabolism proton leak

A first key fact (see Brand, 1995, 1997 Rolfe and Brown, 1997) is that in isolated mitochondria, this proton leak is readily demonstrable in state 4 (all requirements for mitochondrial metabolism present except ADP) but the leak is mainly abolished, or at least, becomes harder to demonstrate on transition to state 3 (ADP-... 

Robin, E.D., B.J. Murphy, and J. Theodore (1984). Coordinate regulation of glycolysis by hypoxia in mammalian cells. J. Cell. Physiol. 118 287-290. Rolfe, D.F., and G.C. Brown (1997). Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol. Rev. 77 731-758. Rolfe, D.F., J.M. Newman, J.A. Buckingham, M.G. Clark, and M.D. Brand (1999). Contribution of mitochondrial proton leak to respiration rate in... 

The control of the respiration process and ATP synthesis shifts as the metabolic state of the mitochondria changes. In an isolated mitochondrion, control over the respiration process in state 4 is mainly due to the proton leak through the mitochondrial inner membrane. This type of control decreases from state 4 to state 3, while the control by the adenine nucleotide and the dicarboxylate carriers, cytochrome oxidase, increases. ATP utilizing reactions and transport activities also increase. Therefore, in state 3, most of the control is due to respiratory chain and substrate transport. 

Rolfe, D., and Brand, M. (1996). Contribution of mitochondrial proton leak to skeletal muscle respiration and to standard metabolic rate. Am. J. Physiol. 271, C1380-C1389. 

A low level of proton leak across the inner mitochondrial membrane occurs in our mitochondria all of the time, and our mitochondria thus are normally partially uncoupled. It has been estimated that more than 20% of our resting metabolic rate is the energy expended to maintain the electrochemical gradient dissipated by our basal proton leak (also referred to as global proton leak). Some of the proton leak results from permeability of the membrane associated with proteins embedded in the lipid bilayer. An unknown amount may result from uncoupling proteins. 

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