Increased Mitochondrial Protein Levels and Bioenergetics in the <i>Musculus Rectus Femoris</i> of Wfs1-Deficient Mice



Eimre, Margus, Paju, Kalju, Peet, Nadezda, Kadaja, Lumme, Tarrend, Marian, Kasvandik, Sergo, Seppet, Joosep, Ivask, Marilin, Orlova, Elite and Koks, Sulev ORCID: 0000-0001-6087-6643
(2018) Increased Mitochondrial Protein Levels and Bioenergetics in the <i>Musculus Rectus Femoris</i> of Wfs1-Deficient Mice. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2018. 3175313-.

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Abstract

Wfs1 deficiency leads to a progressive loss of plasma insulin concentration, which should reduce the consumption of glucose in insulin-dependent tissues, causing a variety of changes in intracellular energy metabolism. Our objective here was to assess the changes in the amount and function of mitochondrial proteins in different muscles of Wfs1-deficient mice. Mitochondrial functions were assayed by high-resolution oxygraphy of permeabilized muscle fibers; the protein amount was evaluated by liquid chromatography tandem mass spectrometry (LC/MS/MS) analysis and mRNA levels of the uncoupler proteins UCP2 and UCP3 by real-time PCR; and citrate synthase (CS) activity was determined spectrophotometrically in muscle homogenates. Compared to controls, there were no changes in proton leak and citrate synthase activity in the heart and <i>m. soleus</i> tissues of Wfs1-deficient mice, but significantly higher levels of both of these factors were observed in the <i>m. rectus femoris</i>; mitochondrial proteins and mRNA of UCP2 were also higher in the <i>m. rectus femoris</i>. ADP-stimulated state 3 respiration was lower in the <i>m. soleus</i>, remained unchanged in the heart, and was higher in the <i>m. rectus femoris</i>. The mitochondrial protein amount and activity are higher in Wfs1-deficient mice, as are mitochondrial proton leak and oxygen consumption in <i>m. rectus femoris</i>. These changes in muscle metabolism may be important for identifying the mechanisms responsible for Wolfram syndrome and diabetes.

Item Type: Article
Uncontrolled Keywords: Animals, Mice, Knockout, Mice, Membrane Proteins, Mitochondrial Proteins, Reverse Transcriptase Polymerase Chain Reaction, Proteomics, Electron Transport, Energy Metabolism, Male, Quadriceps Muscle, Tandem Mass Spectrometry
Depositing User: Symplectic Admin
Date Deposited: 25 Jan 2019 11:41
Last Modified: 14 Oct 2023 09:10
DOI: 10.1155/2018/3175313
Open Access URL: https://www.hindawi.com/journals/omcl/2018/3175313...
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3031794