Proton-leak proteins

Harper, M. E., R. Dent, S. Monemdjou, V. Bezaire, L. Van Wyck, G. Wells, et al. (2002). Decreased mitochondrial proton leak and reduced expression of uncoupling protein 3 in skeletal muscle of obese diet-resistant women. Diabetes 51(8) 2459-66. 

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. 

ROS production, proton leak, and uncoupling protein 3 an interrelated role in sarcopenia ... 

Actually, two types of proton leak may be present at the mitochondrial level namely, basal proton leak and inducible proton leak. The basal type is present in mitochondria within every tissue, and may be related both to the hpid environment of the membrane and to specific proteins such as adenine nucleotide translocase (ANT) (Brand et al, 2005b Shabalina et al., 2006). The inducible type seems to be tightly regulated and is mediated by specific proteins. In skeletal muscle mitochondria, rmcoupling protein 3 (UCP3) plays a significant role in the latter process (Brand et al., 2005). 

Asami, D.K., R.B. McDonald, K. Hagopian, B.A. Horwitz, D. Warman, A. Hsiao, C. Warden and J.J. Ramsey, 2008. Effect of aging, caloric restriction, and uncoupling protein 3 (UCP3) on mitochondrial proton leak in mice. Exp Gerontol. 43, 1069-76. 

Heat stress is an environmental factor responsible for oxidative stress. We reported that reactive oxygen species (ROS) production by mitochondria was significantly increased in skeletal muscle of birds after exposure to heat stress (Mujahid et al., 2007), and that muscle mitochondria from heat-stressed birds also had the higher mitochondrial membrane potential (AT) (M. Kikusato, unpublished data). These results implied that the overproduction of ROS may depend on AT. We also found that heat stress significantly decreased avian uncoupling protein (avUCP) in muscle mitochondria (Mujahid et al., 2009). Therefore, this decrease may contribute to excess ROS production, possibly via a depression of inducible proton leak. To elucidate more precisely the mechanism involved in the overproduction of mitochondrial ROS under heat stress conditions, we have attempted to clarify how heat stress-induced ROS production depends on AT, and to evaluate the effect of avUCP downregulation on the inducible proton leak. 

In transportation, leaks can be found in the proton-sugar symport in bacteria where a protein mediates the transport of protons and sugar across the membrane, and adding a protonophore, a parallel pathway occurs, causing a leak in the transport. 

In an experiment where the state 4 respiration and Ajit - are determined, it is possible therefore to obtain a value for the leak proton conductance of the membrane. Typical values for mitochondria are in the range 0.3-1 nmol H min mg protein-mV of A/ip,+. ... 

Two properties of lysosomal membrane are especially interesting. First, cer- fp tain membrane proteins transport protons across the membrane, thus creating the required acidic environment within the lysosomes. Second, under certain circumstances lysosomal enzymes leak into other parts of the cell. Such an occurrence... 

Several diseases are caused by oxygen damage from the patient s own mitochondria, which are hot spots for ROS generation. In one of these diseases, Leber s hereditary optic neuropathy (LHON), the mitochondrial proteins that carry electrons and pump protons are broken. The first cells to die are the energy-burning optic nerve cells. The cells die because their broken mitochondria leak too many ROS. 

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