Mitochondria lead to new targets for drug discovery

The mitochondria are the body’s power supply. These tiny organelles generate the majority of the adenosine triphosphate (ATP) used by the cells as an energy source. They comprise an outer membrane, an intermembrane space, an inner membrane, cristae which extend the surface area of the inner membrane where energy is generated, and matrix inside containing proteins, ribosomes and the mitochondrial genome. This mtDNA genome, which is passed exclusively down the maternal line, comprises 37 genes, 13 of which code for proteins, and has 16,569 base pairs.

Energy is created via an electron transfer cascade between several complexes embedded in the inner membrane, with redox energy transferred to oxygen. Complex I uses the enzyme NADH dehydrogenase to facilitate the NADH/NAD+ reaction, and Complex II uses succinate dehydrogenase to facilitate succinate/fumarate. Both of these are involved in biochemical electron-generating cascades, passing electrons to Complex III. Complex III moves electrons to Complex IV via cytochrome b-c1 mediation, and Complex IV, mediated by cytochrome c oxidase, is the last step before the energy-generating ATP/ADP reaction that pushes protons into the intermembrane space to create an electrochemical gradient across the inner membrane.

However, if the electrons reduce oxygen too early in the process, reactive oxygen species (ROS) including superoxide are created, putting the mitochondria under oxidative stress. Other important functions of the mitochondria include the regulation of calcium ion levels in the cell, signalling, apoptosis and control of the cell cycle.

Mitochondrial dysfunction can lead to numerous diseases and conditions. Typical symptoms include cardiovascular problems, neurological disorders, loss of vision or hearing, microvascular damage and diabetes. They also have an impact on brain function and cognition.