By: Ryan Ho

In case you still aren’t exactly clear what your mitochondria do, they are pivotal in keeping our body’s cells healthy and functioning well, not just the “powerhouses of the cell”.

Traditionally, mitochondria have been identified primarily for their ability to generate adenosine triphosphate (ATP), or simply put – energy, in our cells. However, over time, research has shown that these essential organelles are heavily involved in a plethora of cellular processes, including programmed cell death, cell growth and differentiation, cell signaling, and even regulation of your calcium levels.

Not to be confused with genetic mitochondrial diseases, mitochondria-related diseases can be caused by 2 distinct mechanisms: mitochondrial dysfunction and dysregulated mitochondrial function.

When your mitochondria don’t work like they used to before, it might lead to serious abnormalities in mitochondrial function, significantly damaging your mitochondria. This leads to what is called mitochondrial dysfunction. It causes our mitochondria to become less efficient, decreasing energy production and increasing damage caused by harmful byproducts of the cellular processes, such as oxidative stress, to our bodies. This can lead to neurodegenerative diseases, aging and senescence among others.

Conversely, dysregulated mitochondrial function is a less severe impairment of mitochondrial function, where the usual control mechanisms for your mitochondrial processes are changed or impaired, but not completely dysfunctional. This process can be better illustrated through the relation to cancer.

Understanding mitochondria’s involvement in diseases that commonly affect us is crucial in creating targeted therapies and treatment strategies for conditions that involve mitochondrial abnormalities.

Cancer

It has been proven that mitochondria are essential for cancer cell survival and growth, and sometimes cancer cells even hijack mitochondria of healthy cells to strategically reprogram their function, to facilitate their survival, growth and proliferation. This dysregulation of our mitochondrial function is usually a consequence of the reprogramming to oncogenic pathways, specific protein expression, or the loss of tumor suppressors. It has proved to be important for tumorigenesis, tumor development, and tumor metastasis.

In the past, scientists mistakenly believed that cancer was specifically characterized by the damaged mitochondria in our bodies, famously encapsulated in the “Warburg Effect”, where it was stipulated that cancer cells use a less efficient way of producing energy even in the presence of oxygen.

However, over the years research has proven how important mitochondrial function is for cancer, as many cancer cells do indeed have functional mitochondria. Experiments that disabled mitochondria have shown that cancer tumor growth can be slowed down this way. Furthermore, animal studies have demonstrated that drugs specifically targeting mitochondrial function can eliminate cancer cells and lessen tumor growth.

Presently, it has been found that mitochondria are active accomplices that help cancer gain an advantage. Cancer cells utilize mitochondria to produce energy for themselves, build new cell parts, and escape from death, rewiring mitochondrial function for their own oncogenic purposes. Additionally, mitochondria could indirectly contribute to cancer relapses and treatment resistance, as cancer stem cells rely heavily on them for their maintenance and survival.

Thus, understanding how mitochondria are reprogrammed in specific tumors is crucial to pinpoint weaknesses that distinguish each cancer type and develop new, targeted cancer therapies.

Neurodegenerative Diseases

On the other hand, mitochondrial dysfunction causes our brain cells to become weak and unable to perform their job properly, leading to their eventual death and in serious cases, neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease.

Because our mitochondria constantly perform numerous tasks, they are especially vulnerable to harm caused by genetic mutations or environmental toxins, particularly in brain neurons. Consequently, scientists believe this vulnerability in our mitochondria creates a vicious cycle during the neurodegenerative disorders, damaging our mitochondria further and worsening the disease and our mitochondrial health.

For instance, in Alzheimer’s disease, the accumulation of amyloid-beta precursor protein creates an energy deficit in our mitochondria, and another protein called amyloid beta builds up excessively in our mitochondria, poisoning them and contributing to oxidative stress, which damages our brain cells in the process.

Imagine your brain cells are like a city, with mitochondria being its power plants, generating the requisite electricity for everything in the city to work. In the neurodegenerative diseases, these power plants are breaking down slowly. Hence, when these power plants are damaged, the city starts to slowly implode, which leads to the disease symptoms.

It is imperative for us to recognize that the future of treating neurodegenerative diseases lies in precise targeting of mitochondrial processes. We must also use these mitochondrial changes as biomarkers to predict the onset of a disease early, to improve diagnosis and intervention strategies.

Aging and Senescence

Similarly, mitochondrial dysfunction determines something familiar to everyone: aging.

As we age, our tissue and organ function declines through 2 key processes: mitochondrial dysfunction and cellular senescence. Both processes work together in a vicious cycle. Our damaged mitochondria exacerbate cellular stress that can trigger senescence, and senescent cells emit harmful signals that further damage mitochondria.

Cellular senescence happens when our cells stop dividing permanently as a result of prolonged stress or damage, causing dysfunctional cells to build up. This promotes tissue damage and inflammation. Accumulation of these senescent cells also damages stem cell environments and plays a key part in age-related diseases.

Aging causes our mitochondria to change shape and acquire structural abnormalities. As a result, our mitochondria become less efficient, reducing ATP production. At the same time the removal of damaged mitochondria is slowing down. Our mitochondria release more harmful byproducts such as reactive oxygen species (ROS), damaging our lipids, proteins and DNA, leading to oxidative stress.

Since I love analogies, as we age, our power generators (mitochondria) become more inefficient and damage our bodies’ tiny houses (cells). There will be times when our tiny houses get so distressed that they go into lockdown (senescence) and release harmful signals that destroy the houses around them (inflammation), exacerbating the problem our power generators face in trying to power our houses.

Following the ever-popular anti-aging trend, our awareness of mitochondrial dysfunction is critical for the discovery of new ways to slow down the processes that make us grow older.

The evidence is crystal clear: your mitochondria are not bystanders in disease detection, prevention, and treatment – they are incredibly important drivers and, more importantly, actionable targets to maintain and improve your health.

Targeting mitochondrial function must be the way forward in revolutionizing disease prevention and treatment.

At Miphic, we are determined to lead the charge with our mitochondrial precision medicine and drug discovery platform, unlocking the potential to target these cellular powerhouses therapeutically and drive healthcare forward.