The mitochondrion is an organelle-like structure found in the cells of living organisms, including humans. Unlike the cell nucleus, it has its own DNA and can reproduce independently. This unique feature suggests that mitochondria were likely once independent organisms that entered into a symbiotic relationship with our cells.

A mitochondrion is a double-membraned organelle, meaning it has both an outer and inner membrane. The outer membrane surrounds the mitochondrion, forming a protective barrier and allowing molecules needed for metabolism to pass through.

The inner membrane is highly folded, forming structures called cristae. These infoldings increase the surface area of the inner membrane and provide space for various biochemical processes, particularly those involved in energy production. Embedded within are the four complexes of the respiratory chain and ATP synthase, which is responsible for energy generation.

Inside the mitochondria is the matrix, a gel-like area containing enzymes and mitochondrial DNA. The matrix plays a role in various metabolic processes, including the citric acid cycle, which contributes to energy production.

After glucose, obtained through food, is metabolized into pyruvate in glycolysis in the cytoplasm, pyruvate is transported into the mitochondrion. The transport of pyruvate into the mitochondrion is facilitated by specific transport proteins in the outer and inner mitochondrial membranes. This process is crucial for continuing glucose metabolism and involving pyruvate in the citric acid cycle, which takes place within the mitochondrion.

Here is the basic process:

• Cytoplasmic reactions: Glycolysis in the cytoplasm generates two molecules of pyruvate from one molecule of glucose. These pyruvate molecules are crucial intermediates that will be further metabolized.
• Transport through the outer mitochondrial membrane: Pyruvate cannot diffuse directly through the inner mitochondrial membrane. Instead, specialized proteins in the outer mitochondrial membrane, known as porins or VDAC (Voltage-Dependent Anion Channels), facilitate the transport.
• Transport through the inner mitochondrial membrane: After passing through the outer membrane, pyruvate must also cross the inner mitochondrial membrane. This step is facilitated by a specific transport protein called pyruvate carrier protein. The transport of pyruvate into the mitochondrion requires energy in the form of ATP.
• Conversion to Acetyl-CoA: Once inside the mitochondrion, pyruvate is converted into acetyl-CoA. This conversion occurs in the matrix through the pyruvate dehydrogenase complex. During this process, carbon dioxide is released, and NADH is produced. The resulting acetyl-CoA can then be further metabolized in the citric acid cycle to eventually generate electrons for the electron transport chain.
• Citric Acid Cycle (Krebs Cycle): The citric acid cycle takes place in the mitochondrial matrix. Here, pyruvate derived from glycolysis is converted into acetyl-CoA. Acetyl-CoA then combines with oxaloacetate to form citrate. Through a series of enzymatic reactions, citrate is converted to isocitrate. NADH and FADH2 are produced through further reactions. The citric acid cycle concludes with the regeneration of oxaloacetate.
• Electron Transport Chain (ETC): The ETC is located in the inner mitochondrial membrane. The energy contained in the form of protons within NADH and FADH2 from the citric acid cycle and other processes is used to transport electrons through a chain of protein complexes (I to IV).
  • Complex I (NADH dehydrogenase): NADH donates electrons to Complex I, which transports them through a series of proteins. Protons are pumped from the matrix into the intermembrane space. Coenzyme Q10, along with cytochrome C, plays a crucial role here.
  • Complex II (Succinate dehydrogenase): FADH2 donates electrons to Complex II, which is directly integrated into the citric acid cycle.
  • Complex III (Cytochrome bc1 complex): Electrons are further passed from Complex I and II to Complex III, where more protons are pumped into the intermembrane space.
  • Complex IV (Cytochrome c oxidase): Electrons are transported to Complex IV, where oxygen is accepted as the final acceptor, forming water. Once again, protons are pumped into the intermembrane space.
• ATP Synthesis: The proton gradient generated by the electron transport is used by ATP synthase. This complex structure allows protons to flow back into the matrix, catalyzing the synthesis of ATP from ADP and inorganic phosphate.

All these processes ensure that the chemical energy stored in nutrients is converted into ATP for cellular energy supply. The smooth functioning of these complex processes is crucial for cell function and, therefore, for the overall health of the organism.

Several factors can impair mitochondrial function. Here are some of the most important ones:

1. Oxidative Stress: Excessive production of reactive oxygen species (ROS) or free radicals can cause oxidative stress in mitochondria. This stress can damage mitochondrial membranes and enzymes, as well as mitochondrial DNA, leading to functional impairments.

2. Genetic Mutations: Mutations in mitochondrial DNA or genes coding for proteins that work in mitochondria can lead to functional impairments and energy deficiency. Some genetic diseases directly affect mitochondria, such as mitochondrial myopathy.

3. Nutrient Deficiencies: A lack of essential micronutrients like B-vitamins, magnesium, selenium, and others can impair mitochondrial function as these nutrients are involved as coenzymes or cofactors in numerous metabolic processes within mitochondria.

4. Toxic Substances: Toxic substances like heavy metals, pesticides, or certain medications can damage mitochondria. These substances can disrupt electron transport or impair ATP production.

5. Metabolic Disorders: Metabolic disorders, such as genetic defects in fatty acid or amino acid metabolism, can hinder energy production in mitochondria.

6. Inflammation: Chronic inflammation can affect mitochondria by increasing the production of reactive oxygen species and directly impairing mitochondrial function.

7. Aging: With age, the efficiency of mitochondria decreases. This age-related loss of mitochondrial function is referred to as mitochondrial aging or mitochondrial dysfunction in aging.

8. Hormonal Changes: Hormonal changes, especially related to insulin resistance or hormonal imbalances, can impair mitochondrial function.

9. Physiological Stress: Intense physical exertion, chronic stress, or trauma can affect mitochondria and lead to temporary or persistent functional impairments.

It's important to note that these factors are often interconnected, and a comprehensive approach to maintaining mitochondrial health typically involves a combination of a healthy diet, adequate exercise, stress management, and avoidance of toxic influences.

Mitochondrial function can be supported through a healthy lifestyle and specific dietary and behavioral practices. Here are some tips to promote mitochondrial function:

• Balanced Diet: Consume a balanced diet rich in antioxidants, vitamins (especially B-vitamins), minerals, and omega-3 fatty acids. Include foods like leafy greens, berries, nuts, seeds, fish, lean meats, and whole grains.
• Regular Exercise: Regular physical activity promotes mitochondrial biogenesis and enhances energy production. Combine endurance and strength training for maximum benefits.
• Intermittent Fasting: Intermittent fasting can improve mitochondrial function and optimize metabolism. Eating intervals allow mitochondria to recover and work more efficiently.
• Healthy Sleep: Ensure sufficient and high-quality sleep, as it is crucial for mitochondrial regeneration. A dark, cool sleep environment and regular sleep schedules can improve sleep quality.
• Stress Management: Chronic stress can affect mitochondria. Practice relaxation techniques such as meditation, yoga, or breathing exercises to reduce stress.
• Avoiding Toxins: Reduce exposure to environmental toxins, such as heavy metals, pesticides, and air pollutants, to minimize mitochondrial damage.
• Hydration: Drink adequate water to support cell function and energy metabolism.
• Supplements: Consult a healthcare provider to determine the need for supplements. Coenzyme Q10, alpha-lipoic acid, magnesium, vitamin D, and omega-3 fatty acids can be supportive.
• Healthy Fats: Consume healthy fats like avocado, olive oil, and fish oil, which provide essential building blocks for cell membranes and energy production.
• Mitochondrial-Targeted Therapies: Some emerging approaches in research focus on mitochondrial-targeted therapies, including compounds that specifically target mitochondria to enhance their function, such as Intermittent Hypoxia/Hyperoxia Training (IHHT).

By following these guidelines, individuals can promote and maintain healthy mitochondrial function, contributing to overall well-being and energy metabolism.