Mitochondria

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A single cellular mitochondrion
Mitochondria are organelles found in all cells that have a nucleus. In the human body, that would be all cells except red blood cells. They generate most of a cell's energy by manufacturing adenosine triphosphate, ATP. Mitochondria have their own independent genome called mitochondrial DNA.

Immunity[edit]

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

In human disease[edit]

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."[1][2] Hepatitis C has also been shown to "fragment host mitochondria".[2]

Parasites such as Toxoplasma gondii have also been shown to modulate host energy metabolism and dysregulate mitochondrial function,[3], as have bacteria [4] such as E. coli, which has been shown to modulate mitochondrial receptor function.[5]

Mitochondrial disease has a high prevalence of fatigue and debilitation.[6]

Chronic fatigue syndrome[edit]

There is evidence of mitochondrial dysfunction in Chronic Fatigue Syndrome patients. Muscle biopsies have shown evidence of mitochondrial degeneration [7], deletions of mitochondrial DNA [8][9], the reduction of mitochondrial activity [8], and Sarah Myhill found measurable mitochondrial dysfunction correlating with severity of illness.[10][11] Myhill also produced improvement by targeting those dysfunctions.[12] Mitochondrial DNA variants correlate with symptoms, symptom clusters & symptom severity.[13]

Mitochondrial disorders can be mistaken for Chronic Fatigue Syndrome.[14]

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.[15]

ME/CFS Research[edit]

In March 2016, it was announced that the ME/CFS Severely Ill, Big Data Study led by doctor Ronald Davis at the Open Medicine Foundation had a significant result in the area of mitochondria. This resulted in the addition of Robert Naviaux (a mitochondrial expert) to the research team.[16] The results have yet to be published, however a second, replication, study is underway with a different patient group.[17]

Potential treatment[edit]

Garth Nicolson has proposed that mitochondrial lipid replacement therapy can ameliorate mitochondrial related fatigue using a proprietary blend of phospholipids called NT Factor.

Courtney Craig has proposed treatment of mitochondrial damage in ME/CFS patients using fasting, caloric restriction and a ketogenic diet.[18]

Notable studies[edit]

Videos[edit]

Learn more[edit]

See also[edit]

Unused Citations[edit]

Armstrong2014 [19] Vermeulen2010 [20] Maes2009 [21] Morris2013 [22]. Morris2014 [23] Meeus2013 [24]

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Citations[edit]

  1. Anand, Sanjeev K; Tikoo, Suresh K (2013-10-24), "Viruses as Modulators of Mitochondrial Functions", Advances in Virology, Advances in Virology, 2013, 2013: –738794, doi:10.1155/2013/738794 
  2. 2.0 2.1 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., PMID 27010100, doi:10.1038/srep23464 
  3. Saric, J; Li, JV; Swann, JR; et al. (8 Nov 2010), "Integrated cytokine and metabolic analysis of pathological responses to parasite exposure in rodents", Journal of proteome research, 9: 2255–2264 
  4. Rudel T, T; Kepp O, O; Kozjak-Pavlovic V, V (October 2010), "Interactions between bacterial pathogens and mitochondrial cell death pathways", Nat Rev Microbiol., PMID 20818415, doi:10.1038/nrmicro2421 
  5. 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., PMID 15533930, doi:10.1074/jbc.M411550200 
  6. Gorman, Gráinne S; Elson, Joanna L; Newman, Jane; et al. (Jul 2015), "Perceived fatigue is highly prevalent and debilitating in patients with mitochondrial disease", Neuromuscular disorders: NMD, 25 (7): 563–566, ISSN 1873-2364, PMID 26031904, doi:10.1016/j.nmd.2015.03.001 
  7. Behan, WMH; More, IAR; Behan, PO (1991), "Mitochondrial abnormalities in the postviral fatigue syndrome", Acta Neuropathologica, 83 (1): 61–65, PMID 1792865 
  8. 8.0 8.1 Vecchiet, L; Montanari, G; Pizzigallo, E; et al. (19 Apr 1996), "Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome", Neuroscience Letters, 208 (2): 117–120, PMID 8859904 
  9. 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 
  10. 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 
  11. Myhill, S; Booth, NE; McLaren-Howard, J (15 Jan 2009), "Chronic fatigue syndrome and mitochondrial dysfunction", Int J Clin Exp Med, 2 (1): 1–16, PMID 19436827 
  12. 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 
  13. 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, ISSN 1479-5876, PMID 26791940, doi:10.1186/s12967-016-0771-6, lay summary 
  14. Galán, Fernando; de Lavera, Isabel; Cotán, David; Sánchez-Alcázar, José A (24 Sep 2015), "Mitochondrial Myopathy in Follow-up of a Patient With Chronic Fatigue Syndrome", J Investig Med High Impact Case Rep, 3 (3), PMID 26904705, doi:10.1177/2324709615607908 
  15. 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, PMID 25934187, doi:10.1016/j.mito.2015.04.005 
  16. Health Rising Forum (19 Mar 2016), End ME/CFS Severe Patient Study Turns to the Mitochondria 
  17. Metabolomic and Chronic Fatigue Syndrome – by Robert Naviaux, MD
  18. 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, PMID 26315446, doi:10.1016/j.mehy.2015.08.013 
  19. Armstrong, CW; McGregor, NR; Butt, HL; Gooley, PR (Oct 2014), Metabolism in chronic fatigue syndrome, PMID 25344988, doi:10.1016/B978-0-12-801401-1.00005-0 
  20. 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, PMID 20937116, doi:10.1186/1479-5876-8-93 
  21. 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 
  22. 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, PMID 24229326, doi:10.1186/1741-7015-11-205 
  23. Morris, G; 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., PMID 24557875, doi:10.1007/s11011-013-9435-x 
  24. 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, PMID 23834645, doi:10.1517/14728222.2013.818657 


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