Mitochondria and our health

By

Dr Ghayur Ayub

 
A few decades ago, physicists concentrating on subatomic particles revolutionised science and introduced quantum mechanics in physics. In recent decades, the biologists focusing on mitochondria of cell are revolutionising the concept of health. They call mitochondria the power house of the cell. Historically, one theory suggests that mitochondrion was a bacterium that got caught in a eukaryotic cell two billion years ago. Usually, when a bacteria is engulfed by another bacteria it is digested. This time, it wasn’t. It survived and started living within the host cell sharing energy symbiotically making an important place for itself. Today, the cell’s life and for that matter our life depends on mitochondria. 

The number of mitochondria in a cell depends on cell’s activity. The more active the cell, the more mitochondria it contains. For example, a cell in heart and brain has about 2000 mitochondria. The number can increase or decrease changing the health of the cell. A high number of healthy mitochondria in a cell keeps us in a state of youth and increases longevity of our life.   

An impressive research by a Canadian researcher Lee Know explains how mitochondria primarily generate energy. According to him, the process of energy passes through three stages: The first stage is called glycolysis which occurs outside mitochondria producing 10% of energy. The second and third stages occur in mitochondria as citric acid cycle and electron transport chain respectively producing 90% of energy. The aim of the process is to transform glucose and oxygen into a high-energy molecule, adenosine triphosphate or ATP from adenosine diphosphate or ADP leaving water and carbon dioxide as by-products. It is akin to respiration at cellular level.

At the level of citric acid cycle, two NADs (nicotinamide adenine dinucleotide); NAD-plus and NAD-h, are created the balance of which keeps metabolic health of the cell. NAD-plus plays essential role in keeping youthfulness and maintaining longevity of the cell.

After passing smoothly through the phases of electron transport chain, 36 ATPs are produced from 1 glucose molecule: 2 from glycolysis; 2 from citric acid cycle; and 32 from electron transport chain. At the end of the process, one phosphate bond of ATP breaks down releasing energy and changing ATP to ADP which takes part afresh in formation of new ATP.

Sometimes, things go wrong and disturbance occurs in the smooth flow of electrons during the transport chain with metabolic consequences. Some factors that can cause the disturbance are; lack of physical activity; sedentary life style; unhealthy diet; eating artificially created coloured food; air pollution; lack of magnesium; eating less fruit or vegetable; consumption of junk food; and overeating when too many ingested calories cannot be consumed.

In such situations, too many electrons are transported which get clogged or even collide with each other causing their spillage during their flow in the chain. The spilled-over electrons get oxidised prematurely and make Free Radicles which are super-oxidised ions and attack the nearby mitochondrial nucleus. These harmful FRs are neutralised by antioxidants which are extracted from three sources. 1) Primary antioxidants, produced endogenously with help of NRF2 gene. 2) Antioxidants from food. 3) Antioxidants from supplements. The beneficial effects of supplementary antioxidants are exaggerated by vendors presenting them as remedy for all ills. In reality, they are good in neutralising the bad FRs. They do not play direct role in preventing or treating diseases such as cardiovascular diseases, diabetes, immune disorders, Alzheimer disease etc or in prolonging life as the vendors claim.

That role is played by two important molecules – PQQ and coenzyme Q10 – which stop clogging the electrons during the transport chain thus preventing the formation of bad FRs. In addition, these two have other beneficial qualities too. For example, both act as antioxidants. PQQ on its own, helps in biogenesis of mitochondria and activates genes that govern mitochondrial protection, reproduction, and repair. It also helps in reducing degenerative processes in damaged neurons thus enhancing memory. It is found in dark chocolate, breast milk, fermented food ect.

While coenzyme Q10 which is found abundantly in heart muscles of animals, protects mitochondrial membrane and optimizes mitochondrial function. Also, it prevents oxidation of cholesterol. It is the oxidised cholesterol which is harmful to health. Doctors put the patients routinely on anti-cholesterol drugs such as Statins without checking the level of co-enzyme Q10. They don’t know that Statins inhibit coenzyme Q10. A fresh look is needed in this respect. Other substances that inhibit coenzyme Q10 are certain antibiotics and toxins produced by pesticides. Having said that, not all FRs are bad. Those generated during exercise act as primary antioxidants switching on genes such as Fox03 which are good for cellular health.

Coming back to ATP, not many cardiologists know that a relaxing muscle needs more ATPs than contracting muscles. For example, in case of heart, the muscles relax in diastole. When sufficient ATPs are not available in diastolic phase because of mitochondrial dysfunction, the left ventricular muscles start compensating by getting hypertrophied thus reducing the Ejection Fraction and decreasing the output of blood. Soon it becomes a vicious cycle leading to congestive heart failure when EF comes down to 35%. That much important mitochondria and ATP are in cardiac activity.

It’s the same story with blood vessels. The clinicians blame endothelial layer of blood vessel for narrowing of lumen by atherosclerosis caused by high level of injurious cholesterol. It is the hypertrophied rigid muscles of blood vessels caused by deficiency of ATPs during the relax phase of the muscles which initiates the process. The damage to endothelium is secondary to thick and rigid muscular walls. 

Similarly, during excessive exercise oxidants are produced and antioxidants are needed to neutralise them. When mitochondria are damaged or dysfunctional because of bad FRs, the cells close the door for glucose entry thus increasing the systemic glucose levels. Not only that, but the membrane shuts fatty acids’ entry too. The clinicians don't measure the level of fatty acids at the time of checking glucose level. The high fatty acid level will tell that the high sugar level is due to dysfunctional mitochondria.

Finally, when dysfunctional mitochondria are not producing optimum energy they go into low energy state called ‘hibernation’ or ‘cell danger response mode’ wherein ATPs are not formed through the normal process of electron transport chain. Instead, two ADPs combine and make one ATP and in the process one adenosine monophosphate or AMP is also produced which is injurious to cell. The cell tries to eliminate AMP wasting more energy by depleting the energy pool and increasing mitochondrial fatigue. The chronic fatigue syndrome we link with adrenaline gland is actually due to fatigued mitochondria.

The role of mitochondria in health matters is going to get its due importance in coming years as Quark got its importance in quantum physics in recent decades. 

The end