Uncoupling Protein 2

Introduction

Mutations involving the mitochondria can lead to varies diseases. One particular disease that involves a 3243G mutation in the mitochondrial DNA-encoded tRNA gene is known as Diabetes Mellitus (DM). The predominant issues seen in patients with this disease is glucose intolerances due to gradual development of pancreatic beta-cell malfunction which can be seen with increased age. Uncoupling proteins are key factors that generates these issues. Low levels of uncoupling proteins (UCPs) can lead to high mitochondrial membrane potentials. These increased potentials favor generation of reactive oxygen species (ROS). Increased ROS levels assist the progress of apoptosis and the differentiation state of pancreatic beta-cells which ultimately lead to inadequate secretion of insulin and an inability to maintain glucose levels. Five UCPs have been discovered in mammals, but UCP1, UCP2 and UCP3 have the biggest roles in DM. UPC1’s underlying determinant of DM is from an imbalance of energy intake and expenditure. Research has also found that polymorphisms and UCP1’s mRNA expressions are highly associated with DM. UCP2, the main focus of this research, is known as a negative regulator of insulin secretion and plays the biggest role in DM generation. The ROS initiate UCP2 which is preceded by decreased beta-cell ATP synthesis and lack of regulation of glucose-stimulating insulin secretion. Polymorphism of UCP2 gene is also correlated with DM. UCP3 is also shown to influence insulin secretion through these beta-cells, but less research has been conducted on these proteins.

History

In 1963, researchers discovered that mitochondria have their own DNA or "blueprint" (mtDNA), which is different than the nuclear DNA (nDNA) found in the cells' nucleus. ^[1] Later, in 1988, mutations of this mitochondria DNA was discovered. Mutations like deletions and point mutations were found in all the mitochondrial disorders.^[2]

Disease

Mitochondria are found in the every cell in the human body and it acts as the "power house" of the cell. The mitochondria is called the "power house" because it converts the food consumtion and oxygen to energy to power the body.

A mitochondrial disorder is caused by the mutation of mitochondrial DNA (mtDNA). This disorder is genetic transmitted from a parent and can be seen from birth or at an older age. These disorders are chronic disorders. Some of this disorders can be seen in figure 1.

Figure 1: Mitochondrial Disorders

The disorder which affects the pancreas is caused by the A3243G mutation which causes diabetes. Bilateral hearing impairment is a symptom carried by the carrier of mitochondrial diabetes. Some other symptoms that can be seen is a change in pigmentation of the retina. ^[3] This mutation can be seen around the age of 38 years old, this disease is age dependent in the fact that over time there is a deterioration of glucose homeostasis. The pattern of inhertitance of this disorder depends on the mitochondria of the mother and can be passed down to both male and female offspring.

Function

Figure 2: Uncoupling Protein 2

This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.