Question

1. Explain why mitochondrial dysfunction can be caused both by mutations in nuclear DNA and by mutations in mitochondrial DNA.

2. Explain the reasons why mitochondrial DNA is prone to mutations (which step of the electron transport chain is the most "dangerous" to DNA?)

3. Describe what is meant by heteroplasmy discussing how it relates to the phenotypic manifestation of a mitochondrial disease

4. Provide examples of the types of tissues/cells that are most likely to be affected by mitochondrial diseases and explain why.

Answer 1

1. Nuclear DNA codes for many mitochondrial protein. So mutation in nuclear DNA also can cause mitochondrial dysfunction.

2. Mitochondrial DNA mutation can be caused by reactive oxygen species (ROS). ROS is produced by electron transport chain. Leakage of electrons from. Complex I and complex III reduces oxygen to hydrogen peroxide. This mutates mtDNA. MtDNA is also prone to mutation because there is no repair mechanism present in mitochondria.

3. When a cell has few mutated mtDNA and some unaltered mt DNA, it is known as heteroplasmy. When mother cell gives mitochondria to daughter cell, different proportion of mutated and non mutated mitochondria will be present in daughter cell. Higher the mutated mtDNA, higher chance of phenotypic expression in daughter cell