{"id":29866,"date":"2021-02-24T12:47:04","date_gmt":"2021-02-24T12:47:04","guid":{"rendered":"https:\/\/wames.org.uk\/cms-english\/?p=29866"},"modified":"2021-02-24T12:47:04","modified_gmt":"2021-02-24T12:47:04","slug":"dysregulated-provision-of-oxidisable-substrates-to-the-mitochondria-in-me-cfs-lymphoblasts","status":"publish","type":"post","link":"https:\/\/wames.org.uk\/cms-english\/dysregulated-provision-of-oxidisable-substrates-to-the-mitochondria-in-me-cfs-lymphoblasts\/","title":{"rendered":"Dysregulated provision of oxidisable substrates to the mitochondria in ME\/CFS lymphoblasts"},"content":{"rendered":"

Dysregulated provision of oxidisable substrates to the mitochondria in ME\/CFS lymphoblasts<\/a>, by Daniel Missailidis, Oana Sanislav, Claire Y Allan, Paige K. Smith, Sarah J Annesley, and Paul R Fisher in<\/span> Int. J. Mol. Sci<\/em>. 2021, 22(4), 2046; 19 February 2021 [doi.org\/10.3390\/ijms22042046]\u00a0 (This article belongs to the Special Issue\u00a0Environmental Sensitivity Illnesses: Mechanisms and Molecular Signatures 2.0)<\/h3>\n

 <\/p>\n

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

Although understanding of the biomedical basis of Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS) is growing, the underlying pathological mechanisms remain uncertain.<\/p>\n

We recently reported<\/a> a reduction in the proportion of basal oxygen consumption due to ATP synthesis<\/a> by Complex V in ME\/CFS patient-derived lymphoblast<\/a> cell lines, suggesting mitochondrial respiratory inefficiency. This was accompanied by elevated respiratory capacity, elevated mammalian target of rapamycin complex 1 (mTORC1) signaling activity and elevated expression of enzymes involved in the TCA cycle, fatty acid \u03b2-oxidation and mitochondrial transport.\u00a0 These and other observations led us to hypothesise the dysregulation of pathways providing the mitochondria with oxidisable substrates.<\/p>\n

In our current study, we aimed to revisit this hypothesis by applying a combination of whole-cell transcriptomics, proteomics and energy stress signaling activity measures using subsets of up to 34 ME\/CFS and 31 healthy control lymphoblast cell lines from our growing library.<\/p>\n

While levels of glycolytic enzymes were unchanged in accordance with our previous observations of unaltered glycolytic rates, the whole-cell proteomes of ME\/CFS lymphoblasts<\/a> contained elevated levels of enzymes involved in the TCA cycle (p = 1.03 \u00d7 10\u22124), the pentose phosphate pathway (p = 0.034, G6PD p = 5.5 \u00d7 10\u22124), mitochondrial fatty acid \u03b2-oxidation (p = 9.2 \u00d7 10\u22123), and degradation of amino acids including glutamine\/glutamate (GLS p = 0.034, GLUD1 p = 0.048, GOT2 p = 0.026), branched-chain amino acids (BCKDHA p = 0.028, BCKDHB p = 0.031) and essential amino acids (FAH p = 0.036, GCDH p = 0.006).\u00a0The activity of the major cellular energy stress sensor, AMPK, was elevated but the increase did not reach statistical significance.<\/p>\n

\"\"<\/p>\n

The results suggest that ME\/CFS metabolism<\/a> is dysregulated such that alternatives to glycolysis<\/a> are more heavily utilised than in controls to provide the mitochondria with oxidisable substrates.<\/p>\n","protected":false},"excerpt":{"rendered":"

Dysregulated provision of oxidisable substrates to the mitochondria in ME\/CFS lymphoblasts, by Daniel Missailidis, Oana Sanislav, Claire Y Allan, Paige K. Smith, Sarah J Annesley, and Paul R Fisher in Int. J. Mol. Sci. 2021, 22(4), 2046; 19 February 2021 … 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":[6612,6613,5627,5211,2782,127,5626,6616,6614,6586,6615,3290],"class_list":["post-29866","post","type-post","status-publish","format-standard","hentry","category-news","tag-amino-acid-catabolism","tag-beta-oxidation","tag-claire-y-allan","tag-daniel-missailidis","tag-glycolysis","tag-mitochondria","tag-oana-sanislav","tag-paige-k-smith","tag-paul-r-fisher","tag-proteomics","tag-sarah-j-annesley","tag-tca-cycle-metabolic-pathways"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p5qkYK-7LI","_links":{"self":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/29866","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=29866"}],"version-history":[{"count":6,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/29866\/revisions"}],"predecessor-version":[{"id":29950,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/posts\/29866\/revisions\/29950"}],"wp:attachment":[{"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/media?parent=29866"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/categories?post=29866"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/wames.org.uk\/cms-english\/wp-json\/wp\/v2\/tags?post=29866"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}