Segalés 2013 Am J Physiol Endocrinol Metab

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Segalés J, Paz JC, Hernández-Alvarez MI, Sala D, Muñoz JP, Noguera E, Pich S, Palacín M, Enríquez JA, Zorzano A (2013) A form of mitofusin 2 (Mfn2) lacking the transmembrane domains and the COOH-terminal end stimulates metabolism in muscle and liver cells. Am J Physiol Endocrinol Metab 305:1208-21.

» PMID: 23941871 Open Access

Segales J, Paz JC, Hernandez-Alvarez MI, Sala D, Munoz JP, Noguera E, Pich S, Palacin M, Enriquez JA, Zorzano A (2013) Am J Physiol Endocrinol Metab

Abstract: Mitofusin 2 (Mfn2), a protein that participates in mitochondrial fusion, is required to maintain normal mitochondrial metabolism in skeletal muscle and liver. Given that muscle Mfn2 is repressed in obese or type 2 diabetic subjects, this protein may have a potential pathophysiological role in these conditions. To evaluate whether the metabolic effects of Mfn2 can be dissociated from its function in mitochondrial dynamics, we studied a form of human Mfn2, lacking the two transmembrane domains and the COOH-terminal coiled coil (ΔMfn2). This form localized in mitochondria but did not alter mitochondrial morphology in cells or in skeletal muscle fibers. The expression of ΔMfn2 in mouse skeletal muscle stimulated glucose oxidation and enhanced respiratory control ratio, which occurred in the absence of changes in mitochondrial mass. ΔMfn2 did not stimulate mitochondrial respiration in Mfn2-deficient muscle cells. The expression of ΔMfn2 in mouse liver or in hepatoma cells stimulated gluconeogenesis. In addition, ΔMfn2 activated basal and maximal respiration both in muscle and liver cells. In all, we show that a form of Mfn2 lacking mitochondrial fusion activity stimulates mitochondrial function and enhances glucose metabolism in muscle and liver tissues. This study suggests that Mfn2 regulates metabolism independently of changes in mitochondrial morphology.

Keywords: Diabetes, Mitochondrial dynamics, Mitochondrial fusion, Mitochondrial respiration

O2k-Network Lab: ES Barcelona Zorzano A


Labels: MiParea: Respiration, mt-Structure;fission;fusion 


Organism: Mouse  Tissue;cell: Skeletal muscle, Liver, Other cell lines  Preparation: Intact cells, Permeabilized tissue  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex IV;cytochrome c oxidase, TCA cycle and matrix dehydrogenases 

Coupling state: LEAK, ROUTINE, OXPHOS, ET  Pathway:HRR: Oxygraph-2k