Uncoupling protein 2 and metabolic diseases

Abstract

Mitochondria are fascinating organelles involved in various cellular-metabolic activities that are integral for mammalian development. Although they perform diverse, yet interconnected functions, mitochondria are remarkably regulated by complex signaling networks. Therefore, it is not surprising that mitochondrial dysfunction is involved in plethora of diseases, including neurodegenerative and metabolic disorders. One of the many factors that lead to mitochondrial-associated metabolic diseases is the uncoupling protein-2, a family of mitochondrial anion proteins present in the inner mitochondrial membrane. Since their discovery, uncoupling proteins have attracted considerable attention due to their involvement in mitochondrial-mediated oxidative stress and energy metabolism. This review attempts to provide a summary of recent developments in the field of uncoupling protein 2 relating to mitochondrial associated metabolic diseases.

UCP2 Overexpression Redirects Glucose into Anabolic Metabolic Pathways

“…We have previously demonstrated that UCP2 is overexpressing at the protein level in several human cancers . The increased levels of UCP2 have been linked to enhanced cell proliferation and tumorigenicity . Furthermore, our results showed that UCP2 overexpression promoted skin tumorigenesis via altering glucose and lipid metabolism, and the key regulators of metabolic processes .…”

“…[22] The increased levels of UCP2 have been linked to enhanced cell proliferation and tumorigenicity. [19,23] Furthermore, our results showed that UCP2 overexpression promoted skin tumorigenesis via altering glucose and lipid metabolism, and the key regulators of metabolic processes. [24,25] As such, UCP2 is thought to be a crucial player in the cascade of molecular and metabolic events associated with carcinogenesis.…”

“…Numerous mitochondrial defects and/or alterations have been suspected to contribute to the pathogenesis and progression of cancer . One such mitochondrial alteration leading to tumor promotion is the amplification of the gene expression for mitochondrial uncoupling protein 2 (UCP2) . UCP2 is an anion transporter present in the inner mitochondrial membrane, whose physiological role is to decrease the mitochondrial membrane potential and reactive oxygen species (ROS) production .…”

“…[16,17] One such mitochondrial alteration leading to tumor promotion is the amplification of the gene expression for mitochondrial uncoupling protein 2 (UCP2). [18,19] UCP2 is an anion transporter present in the inner mitochondrial membrane, whose physiological role is to decrease the mitochondrial membrane potential and reactive oxygen species (ROS) production. [20,21] We have previously demonstrated that UCP2 is overexpressing at the protein level in several human cancers.…”

Association of 45-bp Ins/del Polymorphism of Uncoupling Protein 2 (UCP2) and Susceptibility to Nonalcoholic Fatty Liver and Type 2 Diabetes Mellitus in North-west of Iran

“…On the other hand, one study on 268 obese and 185 nonobese children and adolescents showed that the ins allele of the UCP2 45-bp D/I polymorphism may contribute to low HDL cholesterolemia [35]. Besides, various studies have presented UCP-2 45-bp D/I polymorphism association with higher degree of obesity, insulin resistance, dyslipideamia and lower adjusted metabolic rate [36,37]. Conversely, other studies did not describe any correlation between UCP2 45-bp I/D polymorphism and obesity [38,39].…”