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.

Chronic fatigue syndrome
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. 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

 * 1997, Chronic fatigue syndrome and skeletal muscle mitochondrial function
 * 2015, Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients
 * 2016, Exercise-induced mitochondrial dysfunction: a myth or reality?
 * 2016, Pharmacological NAD-Boosting Strategies Improve Mitochondrial Homeostasis in Human Complex I-Mutant Fibroblasts
 * 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

Learn more

 * CFS - The Central Cause - Mitochondrial Failure
 * Wikipedia - Mitochondrion
 * 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"

Unused Citations
Armstrong2014 Craig2015 Vermeulen2010 Maes2009 Morris2013. Morris2014 Meeus2013