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What Are Mitochondria?
Mitochondria, small organelles within eukaryotic cells, are integral to cellular function. According to the endosymbiotic theory, mitochondria originated from free-living prokaryotes that were assimilated into eukaryotic cells, establishing a symbiotic relationship.
In humans, mitochondria are ubiquitous except in erythrocytes, and they are particularly abundant in cells with high energy demands such as muscle, nervous, sensory, and oocyte cells.
Traditionally known as the “powerhouses” of the cell for their role in energy production through aerobic respiration, recent research underscores mitochondria’s functions beyond ATP generation. They serve as crucial regulators of signal transduction and play essential roles in immunological processes, whereby they are gaining importance as therapeutic targets in disease prevention and treatment.
The Functions of Mitochondria
Energy production, cell metabolism and biosynthesis:
The primary role of mitochondria is to generate ATP, the cell’s energy source, by converting nutrients. This process mainly occurs through pyruvate decarboxylation, the citric acid cycle, and oxidative phosphorylation.
Additionally, mitochondria participate in various metabolic pathways, including fatty acid ß-oxidation, gluconeogenesis, ketone body synthesis, and urea synthesis.
Beyond ATP production, mitochondria contribute to the synthesis of nucleotides, lipids, cholesterol, amino acids, glucose, and heme. This multifaceted involvement elucidates why rapidly dividing cells, such as cancer cells and activated T cells, heavily rely on mitochondrial metabolites for biomass production.
Redox homeostasis
Mitochondria are the main intracellular producers of reactive oxygen species (ROS), a by-product of cellular respiration. While ROS can be involved in cellular signalling in small quantities, they are harmful in high concentrations and can lead to the oxidation of proteins, lipids and DNA as well as other disorders in the organism.
To counteract the damage caused by ROS, mitochondria and cells in general have a complex antioxidant system that includes enzymes such as superoxide dismutase (SOD), glutathione peroxidase and catalase. These enzymes help to convert ROS into less reactive / harmful molecules and thus restore redox homeostasis.
Impaired redox homeostasis, which is associated with oxidative stress and mitochondrial dysfunction, among others, can accelerate cell senescence and contribute to the onset of age-related diseases.
Control of programmed cell death (apoptosis)
Apoptosis refers to programmed cell death, which is essential in the development and maintenance of health. On the one hand, apoptosis serves as a control mechanism to eliminate cells that are no longer needed or harmful (e.g. cancer cells). On the other hand, it serves as a regulatory mechanism, stabilising the number of cells in tissues with a rapid cell proliferation rate so that the tissue does not grow or shrink in excess.
In apoptosis, it is important that no inflammatory reaction is triggered and that no surrounding cells are damaged collaterally.
Mitochondria play an essential role in the initiation of apoptosis by releasing proapoptotic factors that stimulate the activation of caspases and other processes leading to cell death.
Neuroendocrine control
Mitochondria are involved in the synthesis and metabolism of hormones, in particular steroid hormones (glucocorticoids, mineralocorticoids, androgens, oestrogens and progesterone).
For example, cholesterol is converted into pregnenolone in the mitochondria of the adrenal cortex, gonads and placental tissue, among others. This is the first step in the synthesis of steroid hormones, with pregnenolone being a precursor molecule for other steroids.
Mitochondria are also involved in the synthesis of neurotransmitters such as acetylcholine or melatonin. Mitochondrial dysfunctions can therefore be a possible influencing factor in hormone or neurotransmitter-associated diseases and dysfunctions.
The Role of Mitochondria in Immune Regulation
Mitochondria are essential for the initiation and regulation of immune responses. In addition to providing energy to immune cells in the form of ATP, they control other important immunological signalling pathways :
– Production of ROS, which are involved in the elimination of pathogens
– Production of type I interferons, which are important for the antiviral immune response
– Initiation of pro-inflammatory signalling pathways via mitochondrial components (including mtDNA)
· The NF-kB signalling pathway
Mitochondria regulate the NF-kB signalling pathway, which is involved in gene expression and plays an important role in the innate immune response. NF-kB protects certain cells from cell death and stimulates the release of proteins specifically targeted at eliminating harmful bacteria and viruses.
However, in mitochondrial dysfunction, this signalling pathway can be permanently activated and lead to chronic inflammation. Efficient regulation of this signalling pathway is therefore of medical relevance in order to maintain or restore mitochondrial function and immune balance.
– Control of apoptosis of infected cells
Conversely, dysfunctional or damaged mitochondria are associated with inflammatory and autoimmune diseases.
Mitochondrial dysfunction can have a negative impact on the immune system, e.g. by triggering excessive inflammatory processes or failing to recognise pathogens. Conversely, a dysfunctional immune system can disrupt mitochondrial function and thus cellular energy balance
Mitochondrial Dysfunction And Associated Diseases
Mitochondrial disorders are involved in numerous diseases, whereby a distinction is made between primary and secondary mitochondriopathies.
Primary mitochondriopathies are genetically determined and directly linked to mutations in the mitochondrial DNA (mtDNA) or in the nuclear DNA coding for mitochondrial proteins. Examples of primary mitochondriopathies are Leber hereditary optic neuropathy (LHON), chronic progressive external ophthalmoplegia or MELAS syndrome.
Secondary mitochondriopathies are usually acquired in the course of life. Causes and aggravators include:
· Malnutrition and lack of exercise
· Toxins from smoking, heavy metals, chemicals, pesticides, insecticides, solvents
· Electrosmog
· Anaesthetics and medication
· Chronic infections
· Mental and physical stress
· Uncontrolled immune activation / chronic inflammation
· Severe oxidative stress
· Loss of efficiency of the antioxidant systems
· Essential micronutrient deficiencies
· Other factors
Mitochondrial dysfunctions are associated with disorders of ATP production and various metabolic processes, disorders of calcium and iron homeostasis, oxidative stress and uncontrolled inflammation as well as impaired apoptosis.
Dysfunctional mitochondria are therefore involved in numerous multisystem diseases, such as cancer, age-related and neurodegenerative diseases, ME/CFS, autoimmune diseases and metabolic diseases. Mitochondria are thereby becoming a key target in the treatment and prevention of chronic diseases.
Mitochondrial Regulation Through Micro-immunotherapy and Other Therapeutic Measures
As part of personalised, multimodal treatment strategies, micro-immunotherapy can make an important contribution to mitochondrial regulation. The specific micro-immunotherapy formula directed at optimising mitochondrial function is composed of cytokines and nucleic acids in low doses (low & ultra-low doses). Due to its specific composition and sequence, it is aimed at exerting an effect on multiple levels, pursuing the following goals:
· Dampen inflammation and reduce oxidative stress
· Regulate the immune response
· Optimise mitochondrial function
· Balance cellular energy metabolism
Mitochondrial regeneration can also be supported through basic measures such as diet, regular endurance training, good sleep hygiene and stress reduction.
Intermittent fasting, calorie restriction and a ketogenic diet can promote mitochondrial biogenesis (formation of new mitochondria) and mitophagy (removal of old, damaged or non-functioning mitochondria) and improve mitochondrial performance.
In addition, compensating for micronutrient deficiencies or a basic supply of the most important mitotropic substances are further strategies to optimise mitochondrial function and energy production.
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