{"id":22378,"date":"2020-02-20T09:19:05","date_gmt":"2020-02-20T09:19:05","guid":{"rendered":"https:\/\/wames.org.uk\/cms-english\/?p=22378"},"modified":"2020-02-20T09:19:05","modified_gmt":"2020-02-20T09:19:05","slug":"an-isolated-complex-v-inefficiency-dysregulated-mitochondrial-function-in-immortalized-lymphocytes-from-me-cfs-patients","status":"publish","type":"post","link":"https:\/\/wames.org.uk\/cms-english\/an-isolated-complex-v-inefficiency-dysregulated-mitochondrial-function-in-immortalized-lymphocytes-from-me-cfs-patients\/","title":{"rendered":"An isolated complex V inefficiency & dysregulated mitochondrial function in immortalized lymphocytes from ME\/CFS patients"},"content":{"rendered":"

An isolated complex V inefficiency and dysregulated mitochondrial function in immortalized lymphocytes from ME\/CFS patients<\/a>, by Daniel Missailidis, Sarah J Annesley, Claire Y Allan, Oana Sanislav, Brett A Lidbury, Donald P Lewis and Paul R Fisher in<\/span> J. Mol. Sci.<\/em> 2020, 21(3), 1074; [doi.org\/10.3390\/ijms21031074]<\/p>\n

 <\/p>\n

Research abstract:<\/strong><\/h3>\n

Myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS) is an enigmatic condition characterized by exacerbation of symptoms after exertion (post-exertional malaise or \u201cPEM\u201d), and by fatigue whose severity and associated requirement for rest are excessive and disproportionate to the fatigue-inducing activity. There is no definitive molecular marker or known underlying pathological mechanism for the condition.<\/p>\n

\"\"<\/a>Increasing evidence for aberrant energy metabolism suggests a role for mitochondrial dysfunction in ME\/CFS. Our objective was therefore to measure mitochondrial function<\/a> and cellular stress sensing<\/a> in actively metabolizing patient blood cells.<\/p>\n

We immortalized lymphoblasts<\/a> isolated from 51 ME\/CFS patients diagnosed according to the Canadian Consensus Criteria and an age- and gender-matched control group. Parameters of mitochondrial function and energy stress sensing were assessed by Seahorse extracellular flux analysis<\/a>, proteomics<\/a>, and an array of additional biochemical assays.<\/p>\n

As a proportion of the basal oxygen consumption rate (OCR), the rate of ATP synthesis<\/a> by Complex V was significantly reduced in ME\/CFS lymphoblasts, while significant elevations were observed in Complex I OCR, maximum OCR, spare respiratory capacity, nonmitochondrial OCR and \u201cproton leak\u201d as a proportion of the basal OCR. This was accompanied by a reduction of mitochondrial membrane potential, chronically hyperactivated TOR Complex I stress signaling and upregulated expression of mitochondrial respiratory complexes, fatty acid transporters, and enzymes of the \u03b2-oxidation and TCA cycles. By contrast, mitochondrial mass and genome copy number, as well as glycolytic rates and steady state ATP levels were unchanged.<\/p>\n

Our results suggest a model in which ME\/CFS lymphoblasts have a Complex V defect<\/a> accompanied by compensatory upregulation<\/a> of their respiratory capacity that includes the mitochondrial respiratory complexes, membrane transporters and enzymes involved in fatty acid \u03b2-oxidation. This homeostatically returns ATP synthesis and steady state levels to \u201cnormal\u201d in the resting cells, but may leave them unable to adequately respond to acute increases in energy demand as the relevant homeostatic pathways are already activated.<\/p>\n

 <\/p>\n

A short guide to mitochondria and complex V<\/a> (you’ll need to sign in)<\/p>\n

Mitochondria-Powering the Cell-Science Video <\/a><\/p>\n

“The Cellular Equivalent of Chronic Fatigue\u201d Found in ME\/CFS<\/a> – the work of Paul Fisher<\/p>\n","protected":false},"excerpt":{"rendered":"

An isolated complex V inefficiency and dysregulated mitochondrial function in immortalized lymphocytes from ME\/CFS patients, by Daniel Missailidis, Sarah J Annesley, Claire Y Allan, Oana Sanislav, Brett A Lidbury, Donald P Lewis and Paul R Fisher in J. Mol. Sci. … Continue reading →<\/span><\/a><\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[1],"tags":[5627,5628,5211,4354,41,23,168,5626,5209,3270,5210,2814,5629],"class_list":["post-22378","post","type-post","status-publish","format-standard","hentry","category-news","tag-claire-y-allan","tag-complex-v","tag-daniel-missailidis","tag-don-p-lewis","tag-energy-metabolism","tag-lymphocytes","tag-mitochondrial-dysfunction","tag-oana-sanislav","tag-paul-fisher","tag-prof-brett-lidbury","tag-sarah-annesley","tag-seahorse-xf-analyser","tag-torc1"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p5qkYK-5OW","_links":{"self":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/22378","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/comments?post=22378"}],"version-history":[{"count":5,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/22378\/revisions"}],"predecessor-version":[{"id":24523,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/22378\/revisions\/24523"}],"wp:attachment":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/media?parent=22378"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/categories?post=22378"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/tags?post=22378"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}