Mitochondrion

A single mitochondrion

A mitochondrion (plural: mitochondria) is an organelle found in all cells that have a nucleus. In the human body, that would be all cells except red blood cells. Mitochondria generate most of a cell's energy by manufacturing adenosine triphosphate, ATP. Mitochondria have their own independent genome called mitochondrial DNA.

Biogenesis

Mitochondrial biogenesis (the creation of new mitochondria) can be increased via hormesis, the exposure of the body to short-term stressors. Healthy stressors include exercise, fasting, cold, heat and light. Resveratrol may also increase mitochondrial biogenesis.

Infection and immunity

Mitochondria play crucial role in innate immunity, namely through their induction of interferon production and apoptosis through mitochondrial antiviral signaling protein (MAVS). Many viruses, including Coxsackievirus B3, echovirus 7, and enterovirus 71 inhibit interferon induction and evade host immunity by cleaving or downregulating MAVS.

Herpes simplex virus (HSV-1), influenza virus, and poliovirus have all been found to reduce cellular respiration. Hepatitis C reduces aerobic metabolism and upregulates glycolysis.

In human disease

Infection with pathogens, including viruses, bacteria, and parasites, can all induce changes in mitochondrial function and energy metabolism.

Viruses can induce or inhibit mitochondrial processes in order to replicate. "Viruses like Herpes simplex virus 1 deplete the host mitochondrial DNA and some, like human immunodeficiency virus and Hepatitis C Virus, hijack the host mitochondrial proteins to function fully inside the host cell." Hepatitis C has also been shown to "fragment host mitochondria".

Parasites such as toxoplasma gondii have also been shown to modulate host energy metabolism and dysregulate mitochondrial function, as have bacteria such as E. coli (Escherichia coli), which has been shown to modulate mitochondrial receptor function.

Mitochondrial diseases have a high prevalence of fatigue and debilitation, with the severity of disease predicting the level of fatigue; Gorman et al (2015) found the degree of muscle weakness was not related to fatigue severity.

ME/CFS

There is increasing evidence of mitochondrial dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome patients. Muscle biopsies have shown evidence of mitochondrial degeneration, deletions of mitochondrial DNA, the reduction of mitochondrial activity, and Sarah Myhill found measurable mitochondrial dysfunction correlating with severity of illness. Myhill also produced improvement by targeting those dysfunctions. Mitochondrial DNA variants correlate with symptoms, symptom clusters & symptom severity.

Differences in protein expression in ME/CFS including proteins related to mitochondria
Green arrows show increases and red arrows show decreases.
Source: Journal of Translational Medicine 18(1):365 Sweetman et al. 2020. doi: 10.1186/s12967-020-02533-3. PMC7512220.

A small study by Sweetman et al. (2020) found a large number of proteins were over or under expressed in ME/CFS patients compared to controls, with many of those proteins known to be involved in mitochondrial function, oxidative phosphorylation, electron transport chain complexes, and redox regulation. The study supported the model of deficient ATP production in ME/CFS, and also suggesting increased oxidative stress.

Mitochondrial disorders can be mistaken for chronic fatigue syndrome.

There is evidence of genetic risk factors for mitochondrial dysfunction in related diseases such as complex regional pain syndrome, postural orthostatic tachycardia syndrome (POTS), and dysautonomia.

A small study of 20 ME/CFS patients meeting the Canadian Consensus Criteria found that re-activation of Human Herpesvirus-6 caused mitochondria dysfunction and reduced the ATP content of cells.

Notable studies

• 1991, Mitochondrial abnormalities in the postviral fatigue syndrome
• 1995, Unusual pattern of mitochondrial DNA deletions in skeletal muscle of an adult human with chronic fatigue syndrome
• 1996, Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome
• 1997, Chronic fatigue syndrome and skeletal muscle mitochondrial function
• 2005, Targeting of enteropathogenic Escherichia coli EspF to host mitochondria is essential for bacterial pathogenesis: critical role of the 16th leucine residue in EspF
• 2009, Chronic fatigue syndrome and mitochondrial dysfunction
• 2009, Integrated cytokine and metabolic analysis of pathological responses to parasite exposure in rodents
• 2009, Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder
• 2010, Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity
• 2010, Interactions between bacterial pathogens and mitochondrial cell death pathways
• 2012, Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
• 2013, Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) - a clinical audit
• 2013, Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics.
• 2013, Viruses as Modulators of Mitochondrial Functions
• 2013, The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients: peripheral and central mechanisms as therapeutic targets?
• 2014, Metabolism in chronic fatigue syndrome
• 2014, Mitochondrial dysfunctions in myalgic encephalomyelitis/chronic fatigue syndrome explained by activated immuno-inflammatory, oxidative and nitrosative stress pathways
• 2015, Mitoprotective dietary approaches for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Caloric restriction, fasting, and ketogenic diets
• 2015, Mitochondrial Myopathy in Follow-up of a Patient With Chronic Fatigue Syndrome
• 2015, Increased prevalence of two mitochondrial DNA polymorphisms in functional disease: Are we describing different parts of an energy-depleted elephant?
• 2015, Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients
• 2016, Hepatitis C virus NS5A protein cooperates with phosphatidylinositol 4-kinase IIIα to induce mitochondrial fragmentation
• 2016, Exercise-induced mitochondrial dysfunction: a myth or reality?
• 2016, Pharmacological NAD-Boosting Strategies Improve Mitochondrial Homeostasis in Human Complex I-Mutant Fibroblasts
• 2016, Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome
• 2018, Parkin and PINK1 mitigate STING-induced inflammation
• 2020, Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (Full text)
• 2020, An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients - (Full text)
• 2020, A SWATH-MS analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome peripheral blood mononuclear cell proteomes reveals mitochondrial dysfunction - (Full text)

Videos

• "Mitochondria: The Powerhouse of the Cell" by Bozeman Science

See also

• Cellular respiration
• Exercise
• Genetics
• Ketogenic diet
• Mitochondrial antiviral signaling protein (MAVS)
• NADH
• NT Factor
• Robert Naviaux
• Sarah Myhill

Learn more

• CFS - The Central Cause - Mitochondrial Failure

• 2016, Immune System Conserves Energy By Altering Metabolism
• 2016, ME Association to fund fourth study into the role of the mitochondria in ME/CFS
• 2016, ME Association Goes All in on the Mitochondria in Chronic Fatigue Syndrome (ME/CFS)
• 2016, Australian metabolomics study of young women with ME/CFS (CCC)
• 2016, "Mitochondria Man Gets Money UK Goes Mega Chronic Fatigue Syndrome Research Moves Forward"

Citations to add to text

Lodi1997 Armstrong2015 Craig2015 Felici2016 Ostojic2016 Sliter2018 Missailidis2020 .

Vermeulen2010 Maes2009 Morris2013 Morris2014 Armstrong2014 Meeus2013

mitochondria Important parts of the biological cell, with each mitochondrion encased within a mitochondrial membrane. Mitochondria are best known for their role in energy production, earning them the nickname "the powerhouse of the cell". Mitochondria also participate in the detection of threats and the response to these threats. One of the responses to threats orchestrated by mitochondria is apoptosis, a cell suicide program used by cells when the threat can not be eliminated.

mitochondria Important parts of the biological cell, with each mitochondrion encased within a mitochondrial membrane. Mitochondria are best known for their role in energy production, earning them the nickname "the powerhouse of the cell". Mitochondria also participate in the detection of threats and the response to these threats. One of the responses to threats orchestrated by mitochondria is apoptosis, a cell suicide program used by cells when the threat can not be eliminated.

genome an organism's complete set of DNA, including all of its genes

mitochondria Important parts of the biological cell, with each mitochondrion encased within a mitochondrial membrane. Mitochondria are best known for their role in energy production, earning them the nickname "the powerhouse of the cell". Mitochondria also participate in the detection of threats and the response to these threats. One of the responses to threats orchestrated by mitochondria is apoptosis, a cell suicide program used by cells when the threat can not be eliminated.

apoptosis a type of cell death in which a cell, in response to a threat, initiates a series of molecular steps that lead to its orderly death. This is one method the body uses to get rid of unneeded or abnormal cells. This form of cell suicide is also called programmed cell death.

mitochondria Important parts of the biological cell, with each mitochondrion encased within a mitochondrial membrane. Mitochondria are best known for their role in energy production, earning them the nickname "the powerhouse of the cell". Mitochondria also participate in the detection of threats and the response to these threats. One of the responses to threats orchestrated by mitochondria is apoptosis, a cell suicide program used by cells when the threat can not be eliminated.

postural orthostatic tachycardia syndrome (POTS) - A form of orthostatic intolerance where the cardinal symptom is excessive tachycardia due to changing position (e.g. from lying down to sitting up).

somatic An adjective relating to the physical body or physical symptoms. It is often contrasted with the adjective "psychological", which refers to the human mind or mental symptoms. In biology, "somatic cells" refer to all the cells of the body, except those which form an egg or sperm.

cytokine any class of immunoregulatory proteins secreted by cells, especially immune cells. Cytokines are small proteins important in cell signaling that modulate the immune system. (Learn more: me-pedia.org)

coenzyme Q10 (CoQ10) - Coenzyme Q10 (also known as ubiquinone) is found in the mitochondria and, as a component of the electron transport chain, plays an important role in aerobic respiration. The chemically-reduced form of CoQ10 is called ubiquinol.

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

mitochondria Important parts of the biological cell, with each mitochondrion encased within a mitochondrial membrane. Mitochondria are best known for their role in energy production, earning them the nickname "the powerhouse of the cell". Mitochondria also participate in the detection of threats and the response to these threats. One of the responses to threats orchestrated by mitochondria is apoptosis, a cell suicide program used by cells when the threat can not be eliminated.

metabolomics The analysis of the chemical metabolism within cells, tissues or organisms. The term is often used to refer to the full set of metabolites found in a cell in a given environment.