Mitochondrial Diseases at the Molecular Level



Our DNA is made up of a sequence of “A”s “T”s, “G”s and “C”s known as bases. These four bases of DNA have specific pairing partners. An “A” always bonds with a “T” and a “G” always bonds with a “C”. When cells divide and DNA is replicated, there are regulatory checkpoints to ensure proper replication; however, mistakes may sometimes occur. A change in the blueprint (DNA), results in a changed product (protein). This altered protein structure may not function effectively which may be problematic for the mitochondria. After a certain threshold, the mitochondria as a whole may no longer be able to function and eventually lead to mitochondrial disease.

Recall the central dogma of biology. For a more detailed look at this basic principle of biology, click here



Central Dogma



The images below show the effects of genetic changes at the molecular level



Nuclear DNA





Mito MtDNA


The Types of Mutations

1. A common replication error is the point mutation. The point mutation occurs when one these pairing partners switch (i.e. when a “G” pairs with an “A”). This slightly changes the resulting protein.





2. Another category of mutation is the deletion. Here, large scale portions of mitochondrial DNA are deleted, often due to environmental factors in the nucleus such as other genes or due to unknown causes. Large scale deletions means a loss in potentially vital mitochondrial genes, and therefore the effects can be fatal.




  • Kearns-Sayre Syndrome
  • CPEO
  • Alpers’ Disease
  • Pearson’s Syndrome


The following link explains the concept of the above mutations in an animation


3. The third category of mitochondrial DNA mutations is the DNA depletions. Unlike our nucleus which only contains a single copy of our DNA, a single mitochondrion may contain tens of copies of its DNA. Like its namesake, DNA depletion diseases result in a reduction in the number of mitochondrial DNA copies.





  • SUCLA2 related DNA depletion syndrome