Question

Mutations in mitochondrial genes frequently produce diseases that affect the brain and skeletal muscle (mitochondrial encephalomyopathies). Why are these two tissues particularly sensitive to mitochondrial mutations?

Answer 1

Mitochondria are structures within cells that convert the energy from food into a form that cells can use. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA. Mitochondrial genes provide instructions for making enzymes involved in oxidative phosphorylation. Oxidative phosphorylation (OXPHOS) is a process that uses oxygen and simple sugars to create adenosine triphosphate (ATP), the cell's main energy source.

In mitochondrial mutations, because of the variables of inherited mutational load, mosaicism, and genetic drift, the same mtDNA mutation can lead to different clinical outcomes in affected individuals. Post-mitotic tissues such as skeletal muscle, cardiac muscle, brain and peripheral nerves are the most frequently affected by mtDNA pathogenic mutations, due to their high energy requirements.