A form of mitofusin 2 (Mfn2) lacking the transmembrane domains and the COOH-terminal end stimulates metabolism in muscle and liver cells

作者：Segales Jessica; Paz Jose C; Isabel Hernandez Alvarez Maria; Sala David; Munoz Juan Pablo; Noguera Eduard; Pich Sara; Palacin Manuel; Antonio Enriquez Jose; Zorzano Antonio^*

来源：American Journal of Physiology - Endocrinology And Metabolism, 2013, 305(10): E1208-E1221.

DOI：10.1152/ajpendo.00546.2012

• mitochondrial dynamics
• diabetes
• mitochondrial respiration
• mitochondrial fusion

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 (Delta Mfn2). This form localized in mitochondria but did not alter mitochondrial morphology in cells or in skeletal muscle fibers. The expression of Delta Mfn2 in mouse skeletal muscle stimulated glucose oxidation and enhanced respiratory control ratio, which occurred in the absence of changes in mitochondrial mass. Delta Mfn2 did not stimulate mitochondrial respiration in Mfn2-deficient muscle cells. The expression of Delta Mfn2 in mouse liver or in hepatoma cells stimulated gluconeogenesis. In addition, Delta Mfn2 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.

• 出版日期2013-11