Cellular bioenergetics is impaired in patients with chronic fatigue syndrome
Chronic fatigue syndrome (CFS) is a highly debilitating disease of unknown aetiology. Abnormalities in bioenergetic function have been cited as one possible cause for CFS. Preliminary studies were performed to investigate cellular bioenergetic abnormalities in CFS patients. A series of assays were c...
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description | Chronic fatigue syndrome (CFS) is a highly debilitating disease of unknown aetiology. Abnormalities in bioenergetic function have been cited as one possible cause for CFS. Preliminary studies were performed to investigate cellular bioenergetic abnormalities in CFS patients. A series of assays were conducted using peripheral blood mononuclear cells (PBMCs) from CFS patients and healthy controls. These experiments investigated cellular patterns in oxidative phosphorylation (OXPHOS) and glycolysis. Results showed consistently lower measures of OXPHOS parameters in PBMCs taken from CFS patients compared with healthy controls. Seven key parameters of OXPHOS were calculated: basal respiration, ATP production, proton leak, maximal respiration, reserve capacity, non-mitochondrial respiration, and coupling efficiency. While many of the parameters differed between the CFS and control cohorts, maximal respiration was determined to be the key parameter in mitochondrial function to differ between CFS and control PBMCs due to the consistency of its impairment in CFS patients found throughout the study (p≤0.003). The lower maximal respiration in CFS PBMCs suggests that when the cells experience physiological stress they are less able to elevate their respiration rate to compensate for the increase in stress and are unable to fulfil cellular energy demands. The metabolic differences discovered highlight the inability of CFS patient PBMCs to fulfil cellular energetic demands both under basal conditions and when mitochondria are stressed during periods of high metabolic demand. |
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Abnormalities in bioenergetic function have been cited as one possible cause for CFS. Preliminary studies were performed to investigate cellular bioenergetic abnormalities in CFS patients. A series of assays were conducted using peripheral blood mononuclear cells (PBMCs) from CFS patients and healthy controls. These experiments investigated cellular patterns in oxidative phosphorylation (OXPHOS) and glycolysis. Results showed consistently lower measures of OXPHOS parameters in PBMCs taken from CFS patients compared with healthy controls. Seven key parameters of OXPHOS were calculated: basal respiration, ATP production, proton leak, maximal respiration, reserve capacity, non-mitochondrial respiration, and coupling efficiency. While many of the parameters differed between the CFS and control cohorts, maximal respiration was determined to be the key parameter in mitochondrial function to differ between CFS and control PBMCs due to the consistency of its impairment in CFS patients found throughout the study (p≤0.003). The lower maximal respiration in CFS PBMCs suggests that when the cells experience physiological stress they are less able to elevate their respiration rate to compensate for the increase in stress and are unable to fulfil cellular energy demands. The metabolic differences discovered highlight the inability of CFS patient PBMCs to fulfil cellular energetic demands both under basal conditions and when mitochondria are stressed during periods of high metabolic demand.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0186802</identifier><identifier>PMID: 29065167</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Abnormalities ; Adult ; Bioenergetics ; Biology and Life Sciences ; Care and treatment ; Causes of ; Chronic fatigue syndrome ; Complications and side effects ; Electron transport ; Energy Metabolism ; Fatigue ; Fatigue Syndrome, Chronic - metabolism ; Female ; Genetic aspects ; Glucose - metabolism ; Glycolysis ; Humans ; Kinases ; Leukocytes (mononuclear) ; Leukocytes, Mononuclear - metabolism ; Male ; Medicine and Health Sciences ; Middle Aged ; Mitochondria ; Mitochondrial DNA ; Mutation ; Oxidative Phosphorylation ; Patients ; Peripheral blood mononuclear cells ; Phosphorylation ; Physical Sciences ; Physiological aspects ; Reserve capacity ; Respiration ; Stress (physiology)</subject><ispartof>PloS one, 2017-10, Vol.12 (10), p.e0186802-e0186802</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Tomas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Tomas et al 2017 Tomas et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-9ebffc37dced6812fec739126ede76a3475eb2693ba8e872b1381b4db2d514293</citedby><cites>FETCH-LOGICAL-c692t-9ebffc37dced6812fec739126ede76a3475eb2693ba8e872b1381b4db2d514293</cites><orcidid>0000-0002-6471-6281</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655451/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655451/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29065167$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tomas, Cara</creatorcontrib><creatorcontrib>Brown, Audrey</creatorcontrib><creatorcontrib>Strassheim, Victoria</creatorcontrib><creatorcontrib>Elson, Joanna L</creatorcontrib><creatorcontrib>Newton, Julia</creatorcontrib><creatorcontrib>Manning, Philip</creatorcontrib><title>Cellular bioenergetics is impaired in patients with chronic fatigue syndrome</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Chronic fatigue syndrome (CFS) is a highly debilitating disease of unknown aetiology. Abnormalities in bioenergetic function have been cited as one possible cause for CFS. Preliminary studies were performed to investigate cellular bioenergetic abnormalities in CFS patients. A series of assays were conducted using peripheral blood mononuclear cells (PBMCs) from CFS patients and healthy controls. These experiments investigated cellular patterns in oxidative phosphorylation (OXPHOS) and glycolysis. Results showed consistently lower measures of OXPHOS parameters in PBMCs taken from CFS patients compared with healthy controls. Seven key parameters of OXPHOS were calculated: basal respiration, ATP production, proton leak, maximal respiration, reserve capacity, non-mitochondrial respiration, and coupling efficiency. While many of the parameters differed between the CFS and control cohorts, maximal respiration was determined to be the key parameter in mitochondrial function to differ between CFS and control PBMCs due to the consistency of its impairment in CFS patients found throughout the study (p≤0.003). The lower maximal respiration in CFS PBMCs suggests that when the cells experience physiological stress they are less able to elevate their respiration rate to compensate for the increase in stress and are unable to fulfil cellular energy demands. The metabolic differences discovered highlight the inability of CFS patient PBMCs to fulfil cellular energetic demands both under basal conditions and when mitochondria are stressed during periods of high metabolic demand.</description><subject>Abnormalities</subject><subject>Adult</subject><subject>Bioenergetics</subject><subject>Biology and Life Sciences</subject><subject>Care and treatment</subject><subject>Causes of</subject><subject>Chronic fatigue syndrome</subject><subject>Complications and side effects</subject><subject>Electron transport</subject><subject>Energy Metabolism</subject><subject>Fatigue</subject><subject>Fatigue Syndrome, Chronic - metabolism</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Glucose - metabolism</subject><subject>Glycolysis</subject><subject>Humans</subject><subject>Kinases</subject><subject>Leukocytes (mononuclear)</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>Mitochondria</subject><subject>Mitochondrial DNA</subject><subject>Mutation</subject><subject>Oxidative Phosphorylation</subject><subject>Patients</subject><subject>Peripheral blood mononuclear cells</subject><subject>Phosphorylation</subject><subject>Physical Sciences</subject><subject>Physiological aspects</subject><subject>Reserve capacity</subject><subject>Respiration</subject><subject>Stress 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Philip</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cellular bioenergetics is impaired in patients with chronic fatigue syndrome</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-10-24</date><risdate>2017</risdate><volume>12</volume><issue>10</issue><spage>e0186802</spage><epage>e0186802</epage><pages>e0186802-e0186802</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Chronic fatigue syndrome (CFS) is a highly debilitating disease of unknown aetiology. Abnormalities in bioenergetic function have been cited as one possible cause for CFS. Preliminary studies were performed to investigate cellular bioenergetic abnormalities in CFS patients. A series of assays were conducted using peripheral blood mononuclear cells (PBMCs) from CFS patients and healthy controls. These experiments investigated cellular patterns in oxidative phosphorylation (OXPHOS) and glycolysis. Results showed consistently lower measures of OXPHOS parameters in PBMCs taken from CFS patients compared with healthy controls. Seven key parameters of OXPHOS were calculated: basal respiration, ATP production, proton leak, maximal respiration, reserve capacity, non-mitochondrial respiration, and coupling efficiency. While many of the parameters differed between the CFS and control cohorts, maximal respiration was determined to be the key parameter in mitochondrial function to differ between CFS and control PBMCs due to the consistency of its impairment in CFS patients found throughout the study (p≤0.003). The lower maximal respiration in CFS PBMCs suggests that when the cells experience physiological stress they are less able to elevate their respiration rate to compensate for the increase in stress and are unable to fulfil cellular energy demands. The metabolic differences discovered highlight the inability of CFS patient PBMCs to fulfil cellular energetic demands both under basal conditions and when mitochondria are stressed during periods of high metabolic demand.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29065167</pmid><doi>10.1371/journal.pone.0186802</doi><tpages>e0186802</tpages><orcidid>https://orcid.org/0000-0002-6471-6281</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Abnormalities Adult Bioenergetics Biology and Life Sciences Care and treatment Causes of Chronic fatigue syndrome Complications and side effects Electron transport Energy Metabolism Fatigue Fatigue Syndrome, Chronic - metabolism Female Genetic aspects Glucose - metabolism Glycolysis Humans Kinases Leukocytes (mononuclear) Leukocytes, Mononuclear - metabolism Male Medicine and Health Sciences Middle Aged Mitochondria Mitochondrial DNA Mutation Oxidative Phosphorylation Patients Peripheral blood mononuclear cells Phosphorylation Physical Sciences Physiological aspects Reserve capacity Respiration Stress (physiology) |
title | Cellular bioenergetics is impaired in patients with chronic fatigue syndrome |
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