Figure 4.

Revised model of the molecular action of UCP2 and UCP3. (Panel A) A model is proposed in which UCP2 and UCP3 account for free fatty acid transport from the mitochondria and mitochondrial Ca²⁺ uniport. It remains to be investigated whether or not both molecular actions of UCP2/UCP3 are independent (A) or interrelated (B) functions of these proteins. (Panel B) Under physiological conditions we propose that UCP2 and UCP3 act as fatty acid carriers and as a fundamental part of the mitochondrial Ca²⁺ uniporter in so optimize and balance mitochondrial metabolic and signalling activity. However, upon nutrition overload, the upregulation of UCP2/UCP3 may disturb this homeostasis by, e.g. forming misfolded UCP proteins [22,23] and/or the lack of other, essential constituents of the mitochondrial Ca²⁺ uniporter [12], resulting in an accumulation of “free” UCP proteins in the membrane that may exhibit basal uncoupling activity, like many other members of the family of mitochondrial anion carrier protein family [15].