Mitochondria is often nicknamed the powerhouse of cells. It consists of a double membrane, DNA, ribosomes, inner membrane surface area fold called cristae, an inner fluid-filled space called the matrix. Mitochondria can self reproduce and can move around cells and change shape. It is also the site of cell respiration.
Mitochondrial DNA makes up only 0.1% of the human genome and is passed down exclusively from mother to child. There are around 1,000 copies of mitochondrial DNA in each cell. A cell is heteroplasmic if it contains a mixture of healthy and faulty mitochondrial DNA. If a cell has no healthy mitochondrial DNA, it is homoplasmic.
Mistakes in mitochondrial DNA affect how well the mitochondria work. Often more than 60% of the mitochondria in a cell will need to be damaged or mutated for mitochondrial diseases like mitochondrial diabetes to emerge. These diseases are often severe and, in some cases, fatal. They affect around every 1 in 5,000 people. These diseases are incurable and largely untreatable. Well until now….
The MRC Mitochondrial Biology Unit at the University of Cambridge found a possible answer in 2018. They used an experimental gene therapy treatment in mice. There they discovered that in heteroplasmic cells, they were successful in targeting and eliminating faulty mitochondrial DNA. Dr. Michal Minczuk shares that this new research does come with a catch, “It would only work in cells with enough healthy mitochondrial DNA to copy themselves and replace the faulty ones that had been removed. It would not work in cells whose entire mitochondria had faulty DNA.”
Pedro Silva-Pinheiro tells us, “This is the first time that anyone has been able to change DNA base pairs in mitochondria in a live animal. It shows that, in principle, we can go in and correct spelling mistakes in defective mitochondrial DNA, producing healthy mitochondria that allow the cells to function properly.” He, along with Dr. Minczuk and their other colleagues, have also used a biological tool known as a mitochondrial base editor. They use this to edit the mitochondrial DNA of live mice. The treatment works by it being delivered into the mouse’s bloodstream using a modified virus. It is then taken in by its cells. The editor looks for unique combinations of the A, C, G, and T molecules that make up DNA. Next changes the DNA base, changing a C to a T. Mitochondrial base editor can correct inevitable ‘spelling mistakes’ that cause the mitochondria to malfunction.
A recent example of how this research had been used is mitochondrial replacement therapy, or other known as three-person IVF. Mitochondrial replacement therapy replaces a mother’s defective mitochondria with a healthy donor’s. However, this process is extraordinarily complex and happens in fewer than one in three cycles in standard IVF.