The significance and mechanism of mitochondrial proton conductance

There is a futile cycle of pump and leak of protons across the mitochondria l inner membrane. The contribution of the proton cycle to standard metaboli c rate is significant, particularly in skeletal muscle, and it accounts for 20% or more of the resting respiration of a rat. The mechanism of the prot on leak is uncertain: basal proton conductance is not a simple biophysical leak across the unmodified phospholipid bilayer. Equally, the evidence that it is catalysed by homologues of the brown adipose uncoupling protein, UCP 1, is weak. The yeast genome contains no clear UCP homologue but yeast mito chondria have normal basal proton conductance. UCP1 catalyses a regulated i nducible proton conductance in brown adipose tissue and the possibility rem ains open that UCP2 and UCP3 have a similar role in other tissues, although this has yet to be demonstrated.