Mitochondrial DNA has been the subject of many studies. Why are mitochondrial diseases so much worse than regular ones?

Question

Think about what the mitochondria does, what is present in it, etc.

Answer 1

Mitochondrial (Mt) diseases can be worse than other genetic diseases because 1) Mt DNA encodes for enzymes that are critical in production of ATP which powers everything in the cell and 2) there is only one version of the genes encoded by DNA unlike nuclear DNA which has two versions (alleles). 3) There are 1000-2000 Mt in a single cell with slight changes to MtDNA which can result in complex mosaicism (mosiac differences in MtDNA).

1. Mt's specific function is to produce ATP, the energy currency of the cell used to power all processes that keep the cell alive. Different pathways are involved and some of the enzymes critical to the production of ATP is coded by Mt DNA. If there is a defect this can have a direct effect on how much unusable energy is available to the cells. All cells rely on Mt but cells that are more energetically demanding such as the brain and muscle cells may be specially vulnerable.
2. Unlike nuclear DNA which has two versions of each gene (one from mom, other from dad) , mtDNA only has one version (We get our Mt and its DNA from mom, thanks mom! ) So if a gene is defective there is no backup version to make up for the defect.
3. Due to numerous Mt in the cell, some Mt lineages may have acquired unique mutations which are passed to daughter cells and hence this can lead to mosaicism and complex manifestation of the disease because some cells have defective MtDNA but others do not.

Answer 2

Mitochondria is the organelle in a typical cell that provides the most amount of energy through aerobic respiration in a combination of the citric acid cycle and the electron transport chain. Almost all the cells in our body use mitochondria, but specifically, cells like muscle cells and nerves that allow us to go through our day to day processes all use high amounts of mitochondria in order to function properly. Now, imagine if there was a defect in all the mitochondria produced in our body. Muscle cells would not function, meaning that daily movement would be impaired, and nerve cells would also lose function, implying a loss in the ability to use almost all of our senses, let alone produce life-saving reflexive actions. Hope this helps! Let me know if more clarification is needed.

Answer 3

The mitochondria is the powerhouse of the cell, making ATP or energy for the body's needs. Any problem with energy production in mitochondria results in mitochondrial disease, which leads to dire consequences. The effect of mitochondrial diseases are worse when the defective mitochondria are present in the brain, muscles or nerves because these structures use more oxygen, and multiple organ failure can result as a consequence.