MITOCHONDRIAL MYOPATHIES

Mitochondrial Myopathies

Mitochondrial Myopathies

Thesis Statement:

The mitochondrial DNA encodes only a few gene products compared to the nuclear DNA. These products, however, play a decisive role in determining cell function. Should this DNA mutate spontaneously or be damaged by free radicals the functionality of the gene products will be compromised. A number of mitochondrial genetic diseases have been identified. Some of these are quite serious and involve the central nervous system as well as muscle, heart, liver and kidney. Aging has been characterized by a gradual increase in base deletions in this DNA. This increase in deletion mutation has been suggested to be the cumulative result of exposure to free radicals.

Introduction

Mitochondria have long been known to serve as central integrators of intermediary metabolism. In this compartment can be found the enzymes of the citric acid cycle, fatty acid oxidation, the initial reaction of the urea cycle, the respiratory chain, and a variety of carriers or transporters. They are the organelles responsible for the synthesis of the high-energy compound, ATP. The synthesis of ATP is coupled to the respiratory chain that produces water by joining two molecules of hydrogen to one molecule of oxygen. This dual synthesis occurs in a stepwise sequence of reactions known as oxidative phosphorylation (OXPHOS). Each of the components of OXPHOS must be present and active. If any one of the many proteins comprising OXPHOS is missing or abnormal due to one or more mutations in the genes encoding these proteins, then OXPHOS will be compromised. The majority of these proteins are encoded by the nuclear genome, synthesized on the ribosomes and imported into the mitochondria. Thirteen of the proteins are encoded by the previous termmitochondrial (mt) previous termDNA. This review will discuss this genome and its expression with respect to aging, free radical damage and degenerative previous termdisease.

Discussion:

Mitochondrial ...