A form of mitofusin 2 (Mfn2) lacking the transmembrane domains and the COOH-terminal end stimulates metabolism in muscle and liver cells
| Autor: | Manuel Palacín, Juan Pablo Muñoz, María Isabel Hernández-Alvarez, Jessica Segalés, Antonio Zorzano, José C. Paz, José Antonio Enríquez, Sara Pich, David Sala, Eduard Noguera |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Physiology Endocrinology Diabetes and Metabolism MFN2 Gene Expression Mice Transgenic Mitochondria Liver Carbohydrate metabolism Mitochondrion Biology Mitochondrial Dynamics GTP Phosphohydrolases Mitochondrial Proteins 03 medical and health sciences Mitofusin-2 Mice 0302 clinical medicine Physiology (medical) medicine Myocyte Animals Humans Protein Isoforms Muscle Skeletal Cells Cultured 030304 developmental biology 0303 health sciences Skeletal muscle Mitochondria Muscle Protein Structure Tertiary Rats Mice Inbred C57BL medicine.anatomical_structure HEK293 Cells Biochemistry mitochondrial fusion Liver Hepatocytes ATP–ADP translocase 030217 neurology & neurosurgery |
| Zdroj: | AJP: Endocrinology and Metabolism; Vol 305 |
| ISSN: | 1522-1555 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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