The Relevance of Mitochondrial Size in Energy Production

Overview

Mitochondria are known as the powerhouses of eukaryotic cells. They are vital to our survival as they generate energy in the form of ATP from the food we eat. This process is known as cellular respiration. In addition, mitochondria store calcium for cell signaling activities, generate heat, and mediate cell growth and death (apoptosis). ¹

When mitochondria stop functioning (mitochondrial dysfunction), the cells are starved of energy. So, depending on the type of cell, symptoms can vary widely. As a general rule, cells that need the largest amounts of energy, such as heart muscle cells and nerves, are affected the most by faulty mitochondria. Mitochondrial dna dysfunction is an important component of different diseases associated with aging, such as Type 2 diabetes ^{2 3 4} and Alzheimer’s disease ^{5 6}. It plays a significant role in chronic fatigue syndrome (C.F.S.), ^{7 8} autism, ^{9 10 11}schizophrenia^{12 13} and bipolar disorder. ^{14 15}

Description of Mitochondria

Mitochondria are small, bean-shaped organelles that are difficult to see under a microscope unless they are stained. Unlike most other organelles, they have two membranes, an outer membrane layer that covers the organelle and contains it like a skin, and an inner membrane. The inner membrane is folded into cristae, which increases the surface area available for chemical reactions to take place. The fluid contained in the center of the mitochondria is called the mitochondrial matrix. The matrix includes the D.N.A. of the mitochondrial genome and the enzymes of the tricarboxylic acid (T.C.A.) cycle (also known as the citric acid cycle, or Krebs cycle), which metabolizes nutrients into by-products the mitochondrion can use for energy production.

Although they appear to be oval-shaped, the structure of mitochondria is continuously changing as a result of mitochondrial fission (breaking apart), mitochondrial morphology, and fusion (coming together) activity. This makes it quite difficult to count the mitochondria in a cell at any given time. 

How many are there in a cell?

The number of mitochondria in a cell varies widely by cell type. For example, mature red blood cells have no mitochondria, whereas liver cells can have more than 2,000. Cells with a high demand for energy tend to have more significant numbers of mitochondria. For example, around 40 percent of the cytoplasm in heart muscle cells is taken up by mitochondria. ¹⁶

The amount of mitochondria in any given cell is continuously in flux. Cells that are actively growing, producing enormous amounts of some products such as di­gestive enzymes, actively transporting materials into the cell, or undergoing movement may display in­creased numbers of mitochondria during periods of activity and reduced numbers during periods of quies­cence.

How Big Are Mitochondria?

Mitochondrial shapes consist of ovoid bodies having a diameter between 0.5 and 1.0 µm and a length of up to 7 µm. Usually, the lower the numbers of mitochondria per cell, the larger are the in­dividual organelles. Inside the cell, mitochondria resemble the long balloons used to create balloon animals. If the mitochondria are too long, they can get tangled. In general, damaged mitochondria are fragmented, round, and swollen, ^{17 18} and such changes in mitochondria  protein are observed in Parkinson’s disease. ^{19 20 21 22}

How are Mitochondrial Sizes Regulated?

The mitochondrial network consists of highly dynamic cellular organelles, with the ability to change size, shape, and position over a few seconds. Many of these changes are due to the complex and co-ordinated processes of mitochondrial fission (a division of a single organelle into two or more independent structures) and fusion (the opposing reaction), which occur synchronously and continually in many cells of the body. It is the balance between these two processes that determine the overall structure of mitochondria in any given cell. ²³Keeping mitochondria at optimal sizes is essential for cellular health and longevity.

Mitochondrial fusion is critical for the maintenance of mitochondrial function. It allows the spreading of mitochondrial D.N.A. throughout the mitochondrial compartment, which optimizes mitochondrial function and prevents the accumulation of mitochondrial mutations during aging. Further, it acts as a “rescue” mechanism that prevents the elimination of damaged mitochondria by mitophagy. ²⁴ A blockage of mitochondrial fusion results in a loss of mitochondrial membrane potential. ²⁵

Mitochondrial fission, on the other hand, plays an essential role in mitochondrial replication and the removal of damaged organelles by selective autophagy. ²⁶

In the absence of mitochondrial fission, ongoing fusion causes the formation of mitochondrial nets with few tubular ends. ^{27 28 29} This may occur as a result of insufficient amounts of the regulating protein, known as dynamin-related protein 1 (Drp1), which causes the mitochondria to get too long and tangled. Too much Drp1 results in excessive mitochondrial fission and too many short mitochondria. ³⁰ Both scenarios result in mitochondrial dysfunction, which given the critical functions of mitochondria in cell homeostasis, can cause a great variety of diseases which can affect almost all the tissues and organs in the body ³¹. This includes neurodevelopmental disorders or neurodegenerative diseases, such as Alzheimer’s or Parkinson’s. ³²

Fission and fusion interact to create a diversity of mitochondrial structures. The arrangements generated include rods of various lengths, sausage string appearance, looped structures, and multiple branched and network arrangements. ³³ The numerous shapes are related to the function of the cells.

How You Can Take Care of Your Mitochondria

The mitochondria are the powerhouses of the mammalian cell and critical for life. However, they are susceptible to nutrient deficiencies, environmental toxins, and oxidative damage, so special care must be taken to protect and nourish them. To work efficiently, mitochondria need to be resilient. Resilience is built through the action and stimulation of mitochondria by hormetic stressors (a mild stressor that helps build resistance to other stressors), including exercise, calorie restriction, extreme cold and heat exposure, red and near-infrared red light exposure, hypoxia, U.V. light, Xenobiotics (like caffeine, nicotine, alcohol and other drugs) as well as dietary phytonutrients.

Diet & Intermittent Fasting

A diet rich in a variety of plant phytonutrients provides the essential micronutrients the body needs for energy production as well as acting as an antioxidant and hormetic stressor responsible for reducing inflammation and initiating mitochondrial growth and biogenesis (the creation of new individual mitochondria). Plant phytonutrients include polyphenols such as:

• resveratrol in red grapes
• sulforaphane in broccoli
• curcumin in turmeric
• E.C.G.C. in green tea
• epicatechins in cacao
• ellagic acid in pomegranates
• carotenoids in tomatoes
• anthocyanins in berries

Although eating a healthy diet is critically important for mitochondrial health, when you eat and how you eat can also affect mitochondrial function. Calorie restriction and time-restricted feeding (TRF) (or intermittent fasting) have been shown to optimize mitochondrial function and extend lifespan. 

The mild stress placed upon the body by not eating enough acts as a hormetic stressor and activates a wide variety of protective pathways within the body, ramping up anti-inflammatory and antioxidant defenses. Fasting for medical purposes has been suggested since the time of ancient Chinese, Greek, and Roman physicians ³⁴. Even Benjamin Franklin has been quoted as saying, “The best of all medicines is resting and fasting.” ³⁵

Carb cycling is also a form of hormesis, and carbohydrate restriction produces ketone bodies, which may have many protective effects. Ketone bodies are an extremely energy-efficient source of fuel. They produce more ATP than glucose. Using ketone bodies for energy decreases the production of damaging free radicals and lowers inflammation ^{36 37}, which can cause severe disease and damage. ³⁸ Ketogenesis improves mitochondrial health by activating the Nrf2 pathway and increasing mitochondrial biogenesis.

Exercise (Anaerobic Exercise)  

Movement has a profound effect on neurotransmitters that regulate wakefulness. When you sit around a lot during the day, your body thinks it is time to rest and will start preparing for sleep. Sitting and inactivity can lead to a decrease in the number and health of mitochondria, thus slowing down metabolism over time. ^{39 40} Exercise signals your body to wake up. Even small, simple actions such as taking short movement breaks and walking more will increase your N.E.A.T. (Non-Exercise Activity Thermogenesis) and keep you alert and energized. For well-trained individuals, including High-Intensity Interval Training (H.I.I.T.), especially in a fasted state, can improve energy levels.

Supplements

Though eating a healthy, phytonutrient-rich diet, exercising regularly, and getting good quality sleep are vitally important for improving energy levels, it is often difficult to do while balancing the demands of life. This is where supplements can play an important role. Studies have shown that combinations of supplements can significantly reduce fatigue and other symptoms associated with mitochondrial damage and can naturally restore mitochondrial function. ⁴¹

N.T. factors phospholipid complex and astaxanthin (a red pigment found in krill and other seafood) are supplements that support the mitochondrial membrane. They play a role in preventing damage to the mitochondrial membrane from oxygen radicals and replacing/repairing damaged membrane tissues. Lipid therapy has proved very effective at reducing fatigue. ^{42 43} In one study, oral administration of N.T. Factor for 12 weeks resulted in a 35.5% reduction in tiredness and a 26.8% increase in mitochondrial function. ⁴⁴

Other supplements include cofactors in mitochondrial energy production, which assist with biological, chemical reactions in the body. These can be vitamins, minerals, or coenzymes that work synergistically with enzymes in the production of ATP (our energy currency) and include magnesium, coenzyme Q10, B vitamins, L-carnitine, creatine, and D-ribose.

Supplements that protect the mitochondria and activate mitochondrial biogenesis are also useful adjuncts to a healthy lifestyle. Amla (or Indian gooseberry), turmeric, alpha-lipoic acid (A.L.A.), and green tea are potent antioxidants that prevent/reduce oxidative damage and decrease inflammation in the mitochondria. Another supplement, PQQ, or pyrroloquinoline quinone, works synergistically with the master antioxidant glutathione (produced by the body) to support mitochondrial function ⁴⁵ and activate mitochondrial biogenesis. ^{46 47}

The ability of cells to produce energy is directly related to the ability of mitochondria to (1) convert the energy from food to reduced nicotinamide adenine dinucleotide (NADH) and (2) transfer electrons from NADH to the electron transport chain and eventually produce ATP. However, the amount of N.A.D. in your body naturally falls with age ⁴⁸, which may impair biological functions important to health and contribute to age-related diseases. It’s believed that increasing N.A.D. through supplementation may improve symptoms and/or delay these conditions. Citrus bioflavonoids, resveratrol, quercetin, N-acetyl-cysteine (N.A.C.), and niacin or nicotinamide all act as precursors that boost levels of NAD+. ^{49 50 51 52}

For more information on these supplements and many others, please read the article titled “The Best Vitamins and Supplements to Fight Fatigue.” 

Conclusion

Mitochondria generate most of the cell’s energy in the form of adenosine triphosphate (ATP) and are thus termed the powerhouse of the cell. Mitochondria are commonly between 0.75 and 3 μm² in the area but vary considerably in size and structure. Their numbers vary by the type and function of the cell they are situated in, and their size and shape are primarily determined by the delicate balance between mitochondrial fission and fusion events.

 As mitochondria are so critical for health and energy production but are also susceptible to nutrient deficiencies and damage, we must protect and nourish them. This can be achieved by practicing good lifestyle habits (such as eating a healthy, phytonutrient-rich diet and exercising regularly) as well as limiting environmental toxins, intermittent fasting, and judiciously using supplements, as required.