Mitochondria have been linked to Parkinson’s disease (PD) for a few decades now… but what are mitochondria? And what do they have to do with PD?
Mitochondria (singular: mitochondrion) are organelles found in cells that help facilitate the production of energy for that cell. The energy appears as adenosine triphosphate (ATP) and is made from the breakdown of glucose (sugar from food). Part of this process is called oxidative phosphorylation wherein electrons, from previous steps of breaking down glucose, pass from one respiratory chain complex to another thus forming an electrochemical gradient that drives the production of ATP. Cellular respiration occurs when oxygen picks up electrons and forms water, without which the system would halt. Additionally, mitochondria also has a significant role in maintaining the cell’s homeostasis through calcium and lipid metabolisms.
The idea the mitochondria dysfunction may be associated with PD came into effect when the injection of 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP) resulted in Parkinson’s-related symptoms (Chen, Turnbull & Reeve, 2019). At the time, MPTP was presumed to be a synthetic heroin but was later classified as a mitochondrial toxin. MPTP is able to cross the blood brain barrier and convert into a cation (MPP+) which targets the respiratory chain complexes in mitochondria from dopaminergic neurons. These respiratory chain complexes were also found to be at a decreased level in Parkinson’s patients and resulted in oxidative stress and irregular calcium homeostasis (Grünewald, Kumar & Sue, 2019). Oxidative stress can be brought on by reactive oxygen species (ROS) that form when electrons leave the respiratory complexes too early, however, ROSs also are present during the natural ageing process. Unfortunately, this causes damage to the cell’s ability to function. The balance between ROS and antioxidants that manage their levels has been shown to be disproportionate in PD patients (Grünewald, Kumar & Sue, 2019).
The loss of motor symptoms that many PD patients experience is thought to be related back to a decrease in dopaminergic neurons (Dias, Junn & Mouradian, 2013). Not only do these neurons function within the cardiovascular and central nervous systems but they produce dopamine – a chemical messenger that is involved in many cellular processes including movement. It is believed that mitochondrial dysfunction and ROS activity contributes to dopaminergic neuron degradation.
Additionally, the protein Parkin was found to be associated with mitochondrial DNA (mtDNA). Parkin is the protein that when mutated results in Parkinson’s disease. Parkin functions to breakdown proteins that have been tagged as unnecessary or damaged including mitochondria. In PD, the ability to degrade damaged mitochondria is impaired suggesting that mutated Parkin is most likely responsible. Also, mtDNA is genetically transferred through mothers it suggests that PD could be passed through mtDNA, however, more research is needed (Grünewald, Kumar & Sue, 2019).
Another protein, PINK1, is necessary for ensuring proper mitochondrial function and works with Parkin. It recognizes ROSs and other genetic mishaps associated with mitochondria and triggers their degradation. PINK1 also stops damaged mitochondria from producing new mitochondria as a form of quality control. PINK1 also has the ability to activate Parkin further demonstrating the connection between PD and mitochondria.
To tie this all together, mutations in Parkin and PINK1 proteins can lead to mitochondrial dysfunction and result in ROS activity which causes oxidative stress and is found in PD patients.
So, now the question is: are researchers looking to target mitochondria for PD treatments?
The answer is yes! Antioxidant therapy is currently in the preclinical study stage. Antioxidants function to counteract ROS and have the potential to stop the accumulation of high levels in the body (Grünewald, Kumar & Sue, 2019). Ursodeoxycholic acid (UDCA) is also at the beginning stages of being studied. It is used for Primary Biliary Cirrhosis (a liver disease) treatment but could help mitochondrial function (Grünewald, Kumar & Sue, 2019). In addition, exercise trials have begun showing results of decreased oxidative stress and improved mitochondrial function – so get your workout on! These are just a few examples of current potential treatments but as more and more research occurs hopefully there will be at least one that becomes a treatment!
Chen, C., Turnbull, D. M., & Reeve, A. K. (2019). Mitochondrial Dysfunction in Parkinson’s
Disease—Cause or Consequence?. Biology, 8(2), 38.
Dias, V., Junn, E., & Mouradian, M. M. (2013). The role of oxidative stress in Parkinson's
disease. Journal of Parkinson's disease, 3(4), 461-491.
Grünewald, A., Kumar, K. R., & Sue, C. M. (2019). New insights into the complex role of
mitochondria in Parkinson’s disease. Progress in neurobiology, 177, 73-93.