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Aid-Vanakova 2019 MiP2019
Coupling states LEAK  + , OXPHOS  +
Diseases Diabetes  + , Other  +
Has abstract [[Image:MITOEAGLE-logo.jpg|left|100px|link
[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MitoEAGLE]] Mutations in Wfs1 gene, which are responsible for synthesis of transmembrane endoplasmatic reticulum (ER) protein wolframin, cause a multi-targeting disease Wolfram syndrome (WS). The first symptom of the WS is diabetes mellitus, followed in most cases by optic atrophy, diabetes insipidus and deafness. Also, link between Wfs1 deficiency and mitochondrial dysfunction have shown, causing neurological degeneration, ataxia and alteration in heart and skeletal muscle performance [1]. WS is accompanied with progressive loss of pancreatic β-cells cell caused by alterations in cellular Ca<sup>2+</sup> signaling related to ER stress and unfolded protein responses [2]. The precise role of wolframin and pathophysiology at organism level is still poorly understood. We used Wfs1KO mice characterized with impaired glucose tolerance and an activated pathway characteristic for metabolic diseases [3]. Aim of the study is to follow alterations in OXPHOS capacity and phosphotransfer networks caused by Wfs1 deficiency in different muscle types: oxidative heart and soleus muscle and glycolytic ''m. rectus femoris'' and ''m. gastrocnemius'' white. Our results showed that all the studied muscles Wfs1KO mouse has a maximal of ADP-dependent respiration rate with glutamate and malate lower than that of wild-type (WT) animals. However, when pyruvate and malate is used as substrate, no significant difference was detected. At the same time the leak state without adenylates is higher in Wfs1KO in most muscles with both complex I substrate combinations used. At the same time respiration rates with succinate were unaffected by Wfs1 deficiency. It indicates to metabolic alterations in supporting of OXPHOS at the level of complex I. Facilitated energy transfer by creatine kinase (CK), adenylate kinase (AK) and other energy transport pathways is governed by the metabolic status of the cell [4]. In Wfs1KO mice heart muscle AK pathway was more active than WT, while the creatine activated respiration is lower than WT. On the contrary, in the glycolytic m. rectus femoris the activity of AK pathway shows a slight decrease in comparison to the control. Results in energy transfer pathways in the heart and skeletal muscles of Wfs1KO mice indicate shift a in the energy pathway preferences. In addition, Wfs1KO mice showed changes in the coupling between OXPHOS and glycolysis in oxidative cardiac and in glycolytic gastrocnemius white muscle. These changes indicate to compensatory mechanism in response to metabolic alterations.
nism in response to metabolic alterations.  +
Has editor [[Plangger M]]  + , [[Tindle-Solomon L]]  +
Has title [[Image:MiPsocietyLOGO.JPG|left|90px|Mitochondrial Physiology Society|MiPsociety]] Adaptation of muscle OXPHOS in developing glucose intolerance - Wfs1 mice model.  +
Instrument and method Oxygraph-2k  +
Mammal and model Mouse  +
MiP area Respiration  + , Genetic knockout;overexpression  +
Pathways N  + , S  +
Tissue and cell Skeletal muscle  + , Heart  +
Was published by MiPNetLab EE Tallinn Kaambre T + , EE Tartu Paju K +
Was submitted in year 2019  +
Was submitted to event MiP2019/MitoEAGLE Belgrade RS +
Was written by Aid-Vanakova J + , Puurand M + , Timohhina N + , Eimre M + , Peet N + , Paju K + , Tepp K + , Kaambre T +
Categories Abstracts
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
07:31:56, 2 September 2019  +
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