Synergy of uncoupling proteins (1 and 2) with mitochondrial Ca2+uptake machinery potentiate mitochondrial uncoupling

Mitochondrial uncoupling proteins UCP1 and UCP2 have a structural homology of app. 60%. They execute their mitochondria uncoupling function through different molecular mechanisms. Non-shivering thermogenesis by UCP1 is mediated through a transmembrane dissipation of the proton motive force to create heat during sym-pathetic stimulation. UCP2, on the other hand, modulates through the interaction with methylated MICU1 the permeability of the cristae junction, which acts as an isolator for the cristae-located mitochondrial membrane potential. In this mini-review, we discuss and compare the recently described molecular mechanism of UCP1 in brown adipose tissue and UCP2 in aged and cancer non-excitable cells that contribute to mitochondrial uncoupling, and the synergistic effects of both UCPs with the mitochondrial Ca2+ uptake machinery.

Automated summary

Mitochondrial uncoupling proteins UCP1 and UCP2 have different molecular mechanisms for executing their mitochondria uncoupling function, with UCP1 dissipating the proton motive force and UCP2 modulating the permeability of the cristae junction. This mini-review discusses the molecular mechanisms of UCP1 in brown adipose tissue and UCP2 in aged and cancer non-excitable cells, and the synergistic effects of both UCPs with the mitochondrial Ca2+ uptake machinery.