The Mighty Mitochondria Jeanne Rosner, MD
Updated: Nov 14, 2019
Think back to your high school biology days. Do you remember learning about the mitochondrion? It is an organelle within all of our cells in the human body. Mitochondria act as the powerhouse of the cell, taking carbohydrates and fats and converting them to energy called ATP, or adenosine triphosphate. Now let’s fast forward to the present day. Science has determined that mitochondria serve a range of functions beyond being the cell’s battery. The current understanding is that mitochondria determine the longevity of our cells, perhaps even how we age and whether chronic diseases will occur. This amazing organelle orchestrates a host of maintenance pathways within our cells, so perhaps maintaining healthy mitochondria is essential to graceful aging and a long lifespan. Let’s look more closely at this wonderfully powerful and important organelle. Here are some fascinating features of mitochondria:
It is believed that mitochondria evolved from bacteria-like microorganisms approximately two billion years ago.
They are small organelles that float freely throughout the cell.
They play a critical role in the generation of metabolic energy for animal cells. This energy is derived from the breakdown of carbohydrates and fatty acids to make ATP through a process called oxidative phosphorylation (glucose + oxygen = energy [in the form of ATP] + water + carbon dioxide + heat).
They contain their own DNA, called mitochondrial DNA, (MtDNA), which means they can make their own proteins, many of which participate in the process of energy production. By contrast, the majority of our cells' proteins are produced by DNA in our cells' nuclei.
MtDNA is subject to mutations (changes) that can be deleterious and contribute to the aging process. There is a higher mutation rate in MtDNA than in nuclear DNA, most likely due to the high amount of oxidative stress that occurs within mitochondria (more on this to follow).
Energy-requiring cells (such as muscle cells, heart muscle cells and brain cells) have more mitochondria—and they keep making more mitochondria. Mitochondria divide and replicate in an independent and dynamic process called simple fission, whereby they multiply more readily when the energy needs of a cell increase.
They make up 10% of our body weight, and normally occupy 2-20% of the volume of a cell, depending on the tissue.
They are essential for calcium balance.
They control the life and death of the cell through various signaling mechanisms. They are the site for programmed cell death, also known as apoptosis.
They are critical for steroid hormone production.
They can generate reactive oxygen species (ROS) that are used in cellular signaling; however, these ROS can also cause oxidative damage.
There are various theories of how mitochondria affect aging and chronic disease:
A prevailing theory is that the primary cause of aging is due to oxidative stress. In this state, mitochondria produce an overabundance of free radicals, or reactive oxygen species (ROS). Normally, when mitochondria oxidize food into energy, ROS are also produced. When that process goes awry and ROS are overproduced and accumulate, it can cause irreversible damage to cellular macromolecules (proteins, lipids and DNA) and cause cellular dysfunction. As such, it is a driving force of aging and a major determinant of lifespan. Under normal conditions, there are antioxidant systems within the cells that help maintain a balance of the ROS and prevent their buildup. However, in situations where there is excessive production of ROS (as an example, due to high dietary consumption of sugar/fructose) and limited cellular antioxidant defense capability, oxidative stress results (see SOULFUL Insight on oxidative stress). In addition, as we age, we lose the ability to repair the excessive damage created by free radicals.
There is another concept referred to as mitohormesis (mitochondrial hormesis). It hypothesizes that repetitive low levels of oxidative stress may trigger an adaptive response in the mitochondria. This adaptation can result in overcoming oxidative stress and may eventually lead to beneficial effects such as an increased lifespan.
Mitochondria are highly dynamic structures. The maintenance of cellular homeostasis (balance) requires the continual elimination of defective mitochondria (termed mitophagy) and the continual generation of new mitochondria. This ongoing removal and regeneration process is necessary for the cell to respond to its physiological/metabolic demands, stress exposure, and intracellular and environmental cues. When this crosstalk between the production of new mitochondria and the removal of defective mitochondria goes awry, various age-related pathologies can occur.
Today, most believe that a combination of many factors leads to mitochondrial dysfunction. These include accumulation of mutated DNA, enhanced oxidative damage, decreased abundance and quality of mitochondria and dysregulation of mitochondrial dynamics.
Mitochondrial dysfunction and disease can affect every system in our body and result in chronic issues such as heart disease with arrhythmias, cardiomyopathies, diabetes, cancer, neurodegenerative diseases such as Parkinson’s and Alzheimer’s, and neurological conditions such as strokes, migraines and muscle issues. There is often decreased mitochondrial function in aged tissues. The link between mitochondrial function and lifespan is complex, and cannot be oversimplified to the single idea that highly active mitochondria increase lifespan.
What can we do to maintain/improve mitochondrial function?
Exercise: When you exercise at high intensity, there is a greater demand for energy, thus triggering the cell to produce more mitochondria (this occurs in your muscles and other cells, too). In addition, as one exercises, free radical stimulation occurs and an increase of ROS ensues. The transient production of oxidative stress/ROS stimulates the mitochondria to repair themselves. This is an example of mitohormesis (described above). Do strength training and high-intensity interval training.
Antioxidants in foods: A variety of antioxidants are naturally abundant in fruits, vegetables, whole grains, nuts and seeds. Perhaps it is the synergy of the various components in whole foods, rather than isolated nutrients, that ultimately yields better health. The whole food is greater than the sum of its parts. Increase your ingestion to a total amount of six to nine cups of fruits and vegetables every day. Aim for a variety and food rich in color. There are likely many additional benefits to eating real, antioxidant-rich food rather than taking an individual nutrient (antioxidant). Numerous studies involving antioxidant supplements have not demonstrated that the supplements are protective in terms of oxidative stress.
Calorie restriction: This causes a reduction in the metabolic rate of an organism, so fewer ROS are produced. It may cause an adaptive response prompted by the specific metabolic alterations of reduced food uptake, and induce mitochondrial hormesis (the adaptive state). One general mechanism of fasting is that it triggers adaptive cellular stress responses, which result in an enhanced ability to cope with more severe stress and counteract disease processes. In some species, this has been proven to extend lifespan. While the evidence is still lacking for humans, it is possible that findings from future studies will discover human benefit.
Nutritional supplements: These are intended to reduce theoretical problems within mitochondria. They are not FDA-approved.
Coenzyme Q10: This antioxidant works to improve mitochondrial function. Our body makes this molecule naturally; however, as we age we do not produce it as efficiently.
Alpha-lipoic acid: This antioxidant also improves metabolism.
Nicotinamide riboside: This is a precursor to vitamin B3. This has effects on energy metabolism and neuroprotection.
Acetyl-L-carnitine: This antioxidant also helps move fatty acids efficiently throughout the cell.
Magnesium: This mineral is associated with hundreds of reactions vital to healthy body functioning including energy production.
Try to limit or avoid:
Arsenic (can be found in drinking water): It can be toxic to mitochondrial DNA.
Bisphenol A, BPA (found in the lining of many cans): It inhibits the enzyme complexes in mitochondria.
Organophosphates: These damage mitochondria.
The mighty mitochondrion is a genuinely fascinating organelle. Keeping it healthy just may be the key to a long and disease-free life.
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