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A single mitochondrion, with exterior and interior membranes.
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[edit | edit source]

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[edit | edit source]

Mitochondria play crucial role in innate immunity, namely through their induction of interferon production and apoptosis through mitochondrial antiviral signaling protein (MAVS).[1] Many viruses, including Coxsackievirus B3, echovirus 7, and enterovirus 71 inhibit interferon induction and evade host immunity by cleaving or downregulating MAVS.[2]

Herpes simplex virus (HSV-1),[3] influenza virus,[3] and poliovirus[4] have all been found to reduce cellular respiration. Hepatitis C reduces aerobic metabolism and upregulates glycolysis.[5]

In human disease[edit | edit source]

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."[6][7]Hepatitis C has also been shown to "fragment host mitochondria".[7]

Parasites such as Toxoplasma gondii have also been shown to modulate host energy metabolism and dysregulate mitochondrial function,[8] as have bacteria[9] such as E. coli (Escherichia coli), which has been shown to modulate mitochondrial receptor function.[10]

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.[11]

Chronic fatigue syndrome[edit | edit source]

There is evidence of mitochondrial dysfunction in chronic fatigue syndrome patients. Muscle biopsies have shown evidence of mitochondrial degeneration,[12] deletions of mitochondrial DNA,[13][14] the reduction of mitochondrial activity,[13] and Sarah Myhill found measurable mitochondrial dysfunction correlating with severity of illness.[15][16] Myhill also produced improvement by targeting those dysfunctions.[17] Mitochondrial DNA variants correlate with symptoms, symptom clusters & symptom severity.[18]

Mitochondrial disorders can be mistaken for chronic fatigue syndrome.[19]

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.[20]

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.[21]

Notable studies[edit | edit source]

Videos[edit | edit source]

See also[edit | edit source]

Learn more[edit | edit source]

Unused Citations[edit | edit source]

Armstrong2014 [34] Craig2015[35] Vermeulen2010 [36] Maes2009 [37] Morris2013 [38]. Morris2014 [39] Meeus2013 [40]

References[edit | edit source]

  1. Yu, Chia-Yi (December 2009). "The Interferon Stimulator Mitochondrial Antiviral Signaling Protein Facilitates Cell Death by Disrupting the Mitochondrial Membrane Potential and by Activating Caspases". Journal of Virology. 
  2. Mukherjee, A (March 2011). "The coxsackievirus B 3C protease cleaves MAVS and TRIF to attenuate host type I interferon and apoptotic signaling". PLoS Pathology. 7. 
  3. 3.03.1 Derakhshan, Mohammed (Aug 1, 2006). "Human herpesvirus 1 protein US3 induces an inhibition of mitochondrial electron transport". Journal of General Virology. 87: 2155–2159. 
  4. Koundouris, A (May 2000). "Poliovirus Induces an Early Impairment of Mitochondrial Function by Inhibiting Succinate Dehydrogenase Activity". Biochemical and Biophysical Research Communications. 271: 610–4. 
  5. Ripoli, Maria (October 2009). "Hepatitis C Virus-Linked Mitochondrial Dysfunction Promotes Hypoxia-Inducible Factor 1α-Mediated Glycolytic Adaptation". Journal of Virology. 
  6. Anand, Sanjeev K; Tikoo, Suresh K (Oct 24, 2013), "Viruses as Modulators of Mitochondrial Functions", Advances in Virology, Advances in Virology, 2013, 2013: –738794, doi:10.1155/2013/738794 
  7. 7.07.1 Siu, GK; Zhou, F; Yu, MK; Zhang, L; Wang, T; Liang, Y; Chen, Y; Chan, HC; Yu, S (March 2016), "Hepatitis C virus NS5A protein cooperates with phosphatidylinositol 4-kinase IIIα to induce mitochondrial fragmentation", Sci. Rep., doi:10.1038/srep23464, PMID 27010100 
  8. Saric, J; Li, JV; Swann, JR; et al. (Nov 8, 2010), "Integrated cytokine and metabolic analysis of pathological responses to parasite exposure in rodents", Journal of proteome research, 9: 2255–2264 
  9. Rudel T, T; Kepp O, O; Kozjak-Pavlovic V, V (October 2010), "Interactions between bacterial pathogens and mitochondrial cell death pathways", Nat Rev Microbiol., doi:10.1038/nrmicro2421, PMID 20818415 
  10. Nagai, T; Abe, A; Sasakawa, C (January 2005), "Targeting of enteropathogenic Escherichia coli EspF to host mitochondria is essential for bacterial pathogenesis: critical role of the 16th leucine residue in EspF", J Bio. Chem., doi:10.1074/jbc.M411550200, PMID 15533930 
  11. Gorman, Grainne S.; Elson, Joanna L.; Newman, Jane; Payne, Brendan; McFarland, Bobby; Newton, Julia L.; Turnbull, Doug M. (2015). "Perceived fatigue is highly prevalent and debilitating in patients with mitochondrial disease". Neuromuscular Disorders. 25 (7): 563–566. doi:10.1016/j.nmd.2015.03.001. 
  12. Behan, WMH; More, IAR; Behan, PO (1991), "Mitochondrial abnormalities in the postviral fatigue syndrome", Acta Neuropathologica, 83 (1): 61–65, PMID 1792865 
  13. 13.013.1 Vecchiet, L; Montanari, G; Pizzigallo, E; et al. (Apr 19, 1996), "Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome", Neuroscience Letters, 208 (2): 117–120, PMID 8859904 
  14. Zhang, C; Baumer, A; Mackay, IR; et al. (Apr 1995), "Unusual pattern of mitochondrial DNA deletions in skeletal muscle of an adult human with chronic fatigue syndrome", Human Molecular Genetics, 4 (4): 751–754, PMID 7633428 
  15. Booth, NE; Myhill, S; McLaren-Howard, J (2012), "Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)", Int J Clin Exp Med, 5 (3): 208–220, PMID 22837795 
  16. Myhill, S; Booth, NE; McLaren-Howard, J (Jan 15, 2009), "Chronic fatigue syndrome and mitochondrial dysfunction", Int J Clin Exp Med, 2 (1): 1–16, PMID 19436827 
  17. Myhill, Sarah; Booth, NE; McLaren-Howard, John (2013), "Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) - a clinical audit.", International Journal of Clinical and Experimental Medicine, PMID 23236553 
  18. Billing-Ross, Paul; Germain, Arnaud; Ye, Kaixiong; et al. (2016), "Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome", Journal of Translational Medicine, 14: 19, doi:10.1186/s12967-016-0771-6, ISSN 1479-5876, PMID 26791940, lay summary 
  19. Galán, Fernando; de Lavera, Isabel; Cotán, David; Sánchez-Alcázar, José A (Sep 24, 2015), "Mitochondrial Myopathy in Follow-up of a Patient With Chronic Fatigue Syndrome", J Investig Med High Impact Case Rep, 3 (3), doi:10.1177/2324709615607908, PMID 26904705 
  20. Boles, RG; Zaki, EA; Kerr, JR; et al. (Jul 2015), "Increased prevalence of two mitochondrial DNA polymorphisms in functional disease: Are we describing different parts of an energy-depleted elephant?", Mitochondrion, 23: 1-6, doi:10.1016/j.mito.2015.04.005, PMID 25934187 
  21. 21.021.1 Schreiner, Philipp; Harrer, Thomas; Scheibenbogen, Carmen; Lamer, Stephanie; Schlosser, Andreas; Naviaux, Robert K.; Prusty, Bhupesh K. (Apr 1, 2020). "Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". ImmunoHorizons. 4 (4): 201–215. doi:10.4049/immunohorizons.2000006. ISSN 2573-7732. PMID 32327453. 
  22. Lodi, R.; Taylor, D. J.; Radda, G. K. (1997). "Chronic fatigue syndrome and skeletal muscle mitochondrial function". Muscle & Nerve. 20 (6): 765–766. ISSN 0148-639X. PMID 9149090. 
  23. Armstrong, Christopher W.; McGregor, Neil R.; Lewis, Neil R.; Butt, Henry L.; Gooley, Paul R. (May 22, 2015). "Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients" (PDF). meaustralia. 
  24. Ostojic, Sergej M. (Aug 1, 2016). "Exercise-induced mitochondrial dysfunction: a myth or reality?". Clinical Science (London, England: 1979). 130 (16): 1407–1416. doi:10.1042/CS20160200. ISSN 1470-8736. PMID 27389587. 
  25. Felici, Roberta; Lapucci, Andrea; Cavone, Leonardo; Pratesi, Sara; Berlinguer-Palmini, Rolando; Chiarugi, Alberto (2015). "Pharmacological NAD-Boosting Strategies Improve Mitochondrial Homeostasis in Human Complex I-Mutant Fibroblasts". Molecular Pharmacology. 87 (6): 965–971. doi:10.1124/mol.114.097204. ISSN 1521-0111. PMID 25788480. 
  26. Sliter, Danielle A.; Martinez, Jennifer; Hao, Ling; Chen, Xi; Sun, Nuo; Fischer, Tara D.; Burman, Jonathon L.; Li, Yan; Zhang, Zhe (Aug 22, 2018). "Parkin and PINK1 mitigate STING-induced inflammation". Nature. doi:10.1038/s41586-018-0448-9. ISSN 0028-0836. 
  27. Andersen, Paul (May 5, 2016). "Mitochondria: The Powerhouse of the Cell". YouTube. Bozeman Science. 
  28. "CFS - The Central Cause: Mitochondrial Failure - DoctorMyhill". Retrieved Sep 6, 2018. 
  29. Marker, Kara (Jul 10, 2016). "Immune System Conserves Energy By Altering Metabolism". LabRoots. Retrieved Sep 6, 2018. 
  30. "ME Association to fund fourth study into the role of the mitochondria in ME/CFS | 10 March 2016". Retrieved Sep 6, 2018. 
  31. Morten, Karl (Mar 2016). "ME Association Goes All in on the Mitochondria in Chronic Fatigue Syndrome (ME/CFS)". Health Rising's Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia Forums. Retrieved Sep 6, 2018. 
  32. Nimmo, Sasha (Jul 6, 2016). "Australian metabolomics study of young women with ME/CFS (CCC)". ME Australia. Retrieved Sep 6, 2018. 
  33. Johnson, Cort (May 19, 2016). "The Mitochondria Man Gets His Money and The UK Goes MEGA: ME/CFS Research Moving Forward - Health Rising". Health Rising. Retrieved Sep 6, 2018. 
  34. Armstrong, CW; McGregor, NR; Butt, HL; Gooley, PR (Oct 2014), "Metabolism in chronic fatigue syndrome", Adv Clin Chem, 66: 121-72, doi:10.1016/B978-0-12-801401-1.00005-0, PMID 25344988 
  35. Craig, Courtney (Nov 2015), "Mitoprotective dietary approaches for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Caloric restriction, fasting, and ketogenic diets", Medical Hypotheses, 85 (5): 690-693, doi:10.1016/j.mehy.2015.08.013, PMID 26315446 
  36. Vermeulen, RC; Kirk, RM; Visser, FC; Sluiter, W; Scholte, HR (October 2010), "Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity", Journal of Translational Medicine, doi:10.1186/1479-5876-8-93, PMID 20937116 
  37. Maes, M; Mihaylova, I; Kubera, M; Uytterhoeven, M; Vrydags, N; Bosmans, E (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", Neuro Endocrinol Lett., PMID 20010505 
  38. Morris, G; Maes, M (September 2013), "Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics.", BMC Med, doi:10.1186/1741-7015-11-205, PMID 24229326 
  39. Morris, Gerwyn; Maes, Michael (March 2014), "Mitochondrial dysfunctions in myalgic encephalomyelitis/chronic fatigue syndrome explained by activated immuno-inflammatory, oxidative and nitrosative stress pathways", Metab Brain Dis., doi:10.1007/s11011-013-9435-x, PMID 24557875 
  40. Meeus, M; Nijs, J; Hermans, L; Goubert, D; Calders, P (September 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?", Expert Opin Ther Targets, doi:10.1517/14728222.2013.818657, PMID 23834645 

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From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history.