Abstract
Uncoupling proteins (UCPs) are transmembrane proteins members of the mitochondrial anion transporter family present in the mitochondrial inner membrane. Currently, six homologs have been identified (UCP1-6) in mammals, with ubiquitous tissue distribution and multiple physiological functions. UCPs are regulators of key events for cellular bioenergetic metabolism, such as membrane potential, metabolic efficiency, and energy dissipation also functioning as pivotal modulators of ROS production and general cellular redox state. UCPs can act as proton channels, leading to proton re-entry the mitochondrial matrix from the intermembrane space and thus collapsing the proton gradient and decreasing the membrane potential. Each homolog exhibits its specific functions, from thermogenesis to regulation of ROS production. The expression and function of UCPs are intimately linked to diabesity, with their dysregulation/dysfunction not only associated to diabesity onset, but also by exacerbating oxidative stress-related damage. Male infertility is one of the most overlooked diabesity-related comorbidities, where high oxidative stress takes a major role. In this review, we discuss in detail the expression and function of the different UCP homologs. In addition, the role of UCPs as key regulators of ROS production and redox homeostasis, as well as their influence on the pathophysiology of diabesity and potential role on diabesity-induced male infertility is debated.
Highlights
Obesity and diabetes mellitus are perilous health issues that constitute a huge economic burden worldwide
UCP3-dependent reactive oxygen species (ROS) suppression and no differences in the mitochondrial membrane potential were observed, which suggests that UCP3 can modulate ROS production through a membrane potential-independent mechanism
Ob/ob mice lacking Ucp2 had enhanced β-cell responsiveness to glucose, decreased levels of glycemia and restored first phase insulin secretion. These results seem to indicate that obesity-dependent induction of UCP2 in pancreatic β-cells has a pathogenic effect towards the development of insulin resistance and in turn diabetes mellitus
Summary
Obesity and diabetes mellitus are perilous health issues that constitute a huge economic burden worldwide. Obesity and diabetes mellitus are intrinsically related to each other, leading to the term “diabesity” Both conditions are regarded as metabolic diseases due to the impairment of metabolism and augmented levels of reactive oxygen species (ROS), that result in oxidative stress [3]. Ubiquinol transports electrons trough the intermembrane space to complex III, where they are again oxidized to quinones. During the transport of electrons through the respiratory chain, protons are pumped from the matrix into the intermembrane space by complexes I, II, and IV This action creates an electrochemical gradient that is used to (B) convert ADP into ATP, by ATP synthase. UCPs play a central role in regulating the potential of mitochondrial membrane, exhibiting several distinct functions from thermogenesis (dissipating energy in the form of heat) to oxidative phosphorylation or ROS levels regulation [13,18,20]. Tubular epithelial cells, granulosa cells *, theca cells *, endometrium glandular epithelium cells *, uterine glands *, oviduct mucosa epithelial cells *, mammary gland, Putative Function
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