What are mitochondrial mutations?

Within each of your cells are many mitochondria, tiny power plants that convert chemicals from food to ATP, the basic fuel molecule used by your cells to provide energy for life, mostly through an energy-harvesting process called oxidative phosphorylation (OXPHOS). Unlike most other such structures in the cell, mitochondria have their own genes (DNA). With aging, more and more of our cells become taken over by mitochondria with damaged (mutated) genes, leading to dysfunction.

How does the damage set in?

OXPHOS generates a small number of toxic molecules called free radicals as a natural byproduct of energy production. Among the problems that they cause, free radicals damage the mitochondrial DNA, leading to mutations that turn off energy production through OXPHOS. Once they have suffered such mutations, DNA-damaged, non-OXPHOS mitochondria eventually take over the entire mitochondrial population of a cell. By the time you are old, perhaps 1% of your cells are in this state of being taken over by non-OXPHOS mitochondria.

Resultant diseases

The abnormal energy metabolism taking place in cells taken over by mutant mitochondria spreads free radical damage throughout the rest of the body. This does direct damage to our cells, DNA, and protein, and causes the body’s metabolic processes to become deregulated, as they normally follow the balance of free radicals as a way of deciding how to govern their metabolism. A chronic excess of free radicals from mutant mitochondria therefore impairs the ability of the body to properly regulate their internal and external environment.

Solution

Scientists have proposed an engineering solution to this problem. The approach is to get to the root, and restore normal energy production in the cells by making the OXPHOS process working again. This can be done by either putting backup copies of mitochondrial DNA into the nucleus, so that unmutated copies of mitochondrial genes are always available to keep OXPHOS going; or ensuring that the necessary proteins can travel from the nucleus back into the mitochondria where they are needed.