Mitochondrial Diseases

Mitochondria are intracellular organelles that play a critical role in cellular metabolism. Mitochondria contain the electron transport chain, which transfers electrons to oxygen by means of a process called oxidative phosphorylation. This process releases energy for the production of adenosine triphosphate (ATP) by forming a pH and electrical gradient (called the chemiosmotic gradient) across the inner mitochondrial membrane. In addition to oxidative phosphorylation, the mitochondria fulfill a number of other functions, including the following:

• Make ATP for cellular energy
• Metabolize fats, carbohydrates, and amino acids
• Interconvert carbohydrates, fats, and amino acids
• Synthesize some proteins
• Reproduce themselves (replicate)
• Participate in apoptosis
• Make free radicals

Of these functions apoptosis is particularly important in development and disease. However, human disease may result from impairment of any of these functions.

Mitochondria are inherited from the mother, but not from the father. In the process of egg formation, there is thought to be a "bottleneck" in mitochondrial number, such that the unfertilized egg may have as few as 1,000 mitochondria. This number increases 100-fold after the ovum is fertilized. The mitochondria contain their own DNA, mitochondrial or mtDNA, and during development there may be selective amplification of some of these mtDNA molecules, leading to increases or decreases in the presence of mutated mtDNAs.

Figure 1. This figure provides an overview of the electron transport chain (ETC). Three defects causing Leigh's disease are highlighted above (purple boxes), with the percentage of cases due to these defects indicated. Numbers of nuclear and mitochondrial DNA (mtDNA) genes encoding the human ETC complexes are listed.