**Author details**

in respiratory chain causes dissipation of energy of oxidation as heat. Besides adaptive thermogenesis, uncoupling of respiration allows continuous reoxidation of coenzymes that are essential to metabolic pathways [203], prevents inhibition of mitochondrial respiration from

The activity of UCPs requires ubiquinone as a cofactor [205] and is regulated by two ligands. UCP1 is activated by fatty acids and inhibited by purine nucleoside di- and triphosphates. UCP2 and 3 can be activated by fatty acid and are less sensitive to purine inhibition. There are not many findings about UCP4 and 5 regulation; however, they were reported to be GDPsensitive [206]. The mechanism of proton transport is still controversial. The UCP is referred to act as a pure proton transporter activated by fatty acids, while by other mechanism, UCP facilitates protonated fatty acid transbilayer movements, flip-flop, to the matrix where they release the proton and are then transported back to the IMS by UCP [199, 206]. Consistently with transport of fatty acid anion, UCP1 was shown to transport a variety of ions, suggesting

As has already been mentioned, the physiological function of UCP1 is the production of heat in brown adipocytes. The UCP1 induction is influenced by thyroid hormones and sympathetic nerves and therefore also by drugs activating adrenoceptors [203]. Capsaicin was found to increase levels of all UCPs [206]. A mutation in gene encoding UCP1 is associated to dia-

Although, UCP2 and 3 are not involved in thermogenesis, polymorphisms in the coding region of the *UCP*2 gene are associated with the level of energy expenditure during sleep [209]. These two members reduce ROS formation by mild uncoupling [208] and related to function to decrease mitochondrial oxidative stress load and transport fatty acid peroxides to MOM [210]. Cytokines and thyroid hormone upregulate UCP2 and UCP3 [211]. Thus, physiological response of macrophages is lowering the UCP levels and enhancing the ROS production. Moreover, UCP2 was proposed to act as carrier for the superoxide anion [205]. The expression of UCP2 is induced under starvation when there are elevated levels of fatty acid in the circulation. The expression of UCP3 increases during fasting [212]. In leptin-induced lipolysis, fatty acids are not exported to the liver but are oxidized in adipocytes, where UCP2 initiates fat oxidation that is not associated with energy-requiring processes [213]. Pharmacological inhibition and genetic mutations in UCP2 and UCP3 have been shown to reverse damaging consequences of obesity and diabetes-induced pancreatic β-cell dysfunction [214, 215].

UCP4 and 5 have been shown to be upregulated by oxidative stress, while insulin downregulates their levels [216]. Mutations in *UCP*4 gene have been linked to schizophrenia [217]. For all UCPs, a continuity of upregulation of the expression and incidence of tumor diseases has

As it follows from this review, the proper course of metabolic processes in the mitochondria requires direction of transport systems to the needs of the organism. The activities of transporters can be regulated differently by hormones, phosphorylation and dephosphorylation,

excessive ATP production, and decreases ROS formation [204].

betic retinopathy [208].

270 Mitochondrial Diseases

been described [202].

**10. Conclusion**

that UCP1 is a hydroxyl anion transporter rather than a proton carrier [207].

Janka Vašková1 \*, Jozef Firment2 and Ladislav Vaško1

\*Address all correspondence to: janka.vaskova@upjs.sk

1 Department of Medical and Clinical Biochemistry, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, Košice, Slovak Republic

2 1st Clinic of Anaesthesiology and Instensive Medicine, Faculty of Medicine, Louis Pasteur University Hospital, Pavol Jozef Šafárik University in Košice, Košice, Slovak Republic
