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Increased mitochondrial protein levels and bioenergetics in the musculus rectus femoris of Wfs1-deficient mice

Eimre, M., Paju, K., Peet, N., Kadaja, L., Tarrend, M., Kasvandik, S., Seppet, J., Ivask, M., Orlova, E. and Kõks, S. (2018) Increased mitochondrial protein levels and bioenergetics in the musculus rectus femoris of Wfs1-deficient mice. Oxidative Medicine and Cellular Longevity, 2018 . pp. 1-12.

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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 m. soleus tissues of Wfs1-deficient mice, but significantly higher levels of both of these factors were observed in the m. rectus femoris; mitochondrial proteins and mRNA of UCP2 were also higher in the m. rectus femoris. ADP-stimulated state 3 respiration was lower in the m. soleus, remained unchanged in the heart, and was higher in the m. rectus femoris. The mitochondrial protein amount and activity are higher in Wfs1-deficient mice, as are mitochondrial proton leak and oxygen consumption in m. rectus femoris. These changes in muscle metabolism may be important for identifying the mechanisms responsible for Wolfram syndrome and diabetes.

Item Type: Journal Article
Publisher: Hindawi Publishing
Copyright: © 2018 Margus Eimre et al.
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