The main mitochondrial structures have been utilized to represent the mechanisms involved in mitochondrial DNA depletion syndrome.
The genes TK2 and DGUOK, which alter the availability of mitochondrial dNTPs essential for mtDNA replication, as well as those that are physically necessary for mtDNA replication, including the polymerase POLG and the helicase TWINKLE, can all be mutated, leading to mitochondrial DNA depletion. Either type of deficiency severely limits the capacity of the patient's cells to replicate mtDNA over time, which causes a decrease in the amount of mtDNA present in the cells and a corresponding decline in oxidative phosphorylation and mitochondrial metabolism.
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