One thing I remember very clearly from grade school was the idea that mitochondria are the powerhouse of a cell. After each successive science class, this same concept popped up time and time again – in different wording, but very much the same meaning.
The human body contains billions of cells, and each of these cells contain hundreds of mitochondria. These bean-shaped structures are considered the powerhouse because it is within these structures that the cell produces most of the energy it needs to function, an energy source called ATP (1).
It seems that these powerhouses might be heavily involved in the way that our bodies handle stress and the mood disorders, like depression, that may develop.
As we go throughout the day, our brains use a particularly large amount of ATP to perform its daily functions. Yet, it is not able to store a sufficient amount of energy in reserve to support these activities. Instead, the brain relies on its cells’ mitochondria to provide a steady supply of energy (2). This could mean that the mitochondria have a significant influence over the way that the brain functions. So, what happens when something goes wrong with the mitochondria?
Well, it turns out that a lot can go wrong. Within the brain, there are a bunch of nerve cells (neurons) that serve as the building blocks of the nervous system. These neurons mainly receive energy through a reaction from the mitochondria called oxidative phosphorylation, or OXPHOS.
If the mitochondria do not provide enough energy to the neurons, then the neurons cannot meet their energy demand. This can lead to different problems in the body, such as impairment in the way that neurons communicate with each other. This has led people to hypothesize that mitochondrial dysfunction may play a role in mood disorders such as depression (2).
The mitochondria have to handle energy demands from a wide variety of reactions ranging from nerve conduction to movement coordination. It especially feels the strain when the body goes through fight-or-flight responses, an instance of high stress. During this response, the mitochondria must produce a significantly higher amount of energy to allow for a faster heartbeat, muscle tension and more. However, this leaves the organelle in a vulnerable state. And mitochondria have rather limited systems in place to repair themselves (1). Various preclinical studies have shown that chronic mild stress can stimulate depressive-like symptoms in mice, in addition to other mitochondrial differences (2).
In addition, researchers have noted that stress can worsen the symptoms of many diseases, including depression and diabetes. Mitochondria could be the potential link between stress and these diseases. One suggestion is that the genetic material from mitochondria triggers an immune response throughout the body. Researchers saw that chronic stress in animal studies led to mitochondrial damage in regions of the brain such as the hippocampus, hypothalamus, and the cortex. Alongside this change, they saw that stress caused the mitochondria to release their DNA into the cell cytoplasm and eventually into the blood (1).
According to a study by researchers at Columbia University, it appears that mitochondrial DNA (mtDNA) can be released in response to psychological stress (kind of like how adrenal glands release the stress hormone cortisol in response to stress). The research team observed a sample of 50 healthy men and women as the study group gave a short speech in defense against a false accusation on camera.
Compared to their base measurements, the subjects’ serum circulating mtDNA levels increased more than twice about 30 minutes after the test. This potentially shows that mtDNA that leaked into the blood could spread stress to other parts of the body (1).
Another study by Swedish scientists found that people with major depression presented higher levels of mtDNA in their blood than their healthy counterparts. In addition, the mtDNA levels continued to rise in patients who did not properly respond to the antidepressant medication.
Furthermore, the leaked mtDNA may induce inflammation in the body. In a 2010 Nature paper, investigators found that released mtDNA could stimulate a pro-inflammatory response from the immune system. Since mtDNA has a bacterial origin and is similarly shaped to bacterial DNA, the body’s immune cells perceive it as a foreign invader.
As a result, the immune cells signal to other white blood cells to mobilize and head to the site of the infection or inflammation. This again supports the idea that psychological stress may provoke widespread inflammation (1). As more research comes out, scientists continue to broach the idea that mitochondrial dysfunction may produce a cascade of effects which result in depression (3).
1. Sheikh, K. (2018). Brain’s dumped DNA may lead to stress, depression. Retrieved from https://getpocket.com/explore/item/brain-s-dumped-dna-may-lead-to-stress-depression?fbclid=IwAR2UFvp6Y04BOea8B4xseQshWHe3DDYk3ABxPR8eE49S_J8lBdukzK45roI
2. Caruso, G., Benatti, C., Blom, J. M. C., Caraci, F. & Tascedda, F. (2019). The many faces of mitochondrial dysfunction in depression: From pathology to treatment. Pharmacol. 10:995. doi: 10.3389/fphar.2019.00995
3. Frontiers. (2018). New theory may explain cause of depression and improve treatments. ScienceDaily. Retrieved www.sciencedaily.com/releases/2018/08/180809112438.htm
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