Page 89 - CIBERDEM2016-ENG

Most relevant scientific articles
• Sebastián D., Sorianello E., Segales J., Irazoki A., Ruiz-Bonilla V., Sala D. et al. Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway. EMBO Journal. 2016.
• Sebastián D., Zorzano A. When MFN2 (mitofusin 2) met autophagy: A new age for old muscles. Autophagy. 2016;:1-2.
• Naon D., Zaninello M., Giacomello M., Varanita T., Grespi F., Lakshminaranayan S. et al. Critical reappraisal confirms that Mitofusin 2 is an endoplasmic reticulum-mitochondria tether. Proceedings of the National Academy of Sciences of the United States of America. 2016;113(40):11249-11254.
• Soro-Arnaiz I., Li Q.O.Y., Torres-Capelli M., Meléndez-Rodríguez F., Veiga S., Veys K. et al. Role of Mitochondrial Complex IV in Age-Dependent Obesity. Cell Reports. 2016;16(11):2991-3002.
• Maria I.H.-A., Kulkarni S.S., Joffraud M., Boutant M., Ratajczak J., Gao A.W. et al. Mfn1 deficiency in the liver protects against diet-induced insulin resistance and enhances the hypoglycemic effect of metformin. Diabetes. 2016;65(12):3552-3560.
Highlights
During 2016, our research group has published 15 scientific articles. Thus, we have shown that mitochondrial protein Mitofusin 2 (Mfn2) is repressed in the skeletal muscle of old mice. This repression is associated with insulin resistance, and reduced muscle mass. In parallel to these observations, knockout mice in which Mfn2 has been specifically deleted in skeletal muscle show impaired glucose tolerance, mitochondrial dysfunction, and muscle atrophy. These results allow us to propose a relevant role of muscle Mfn2 protein in the development of insulin resistance associated with aging, and additionally indicate that mfn2 is a target for the development of new diabetes therapies (Sebastián et al., EMBO Journal 2016).
In addition, our laboratory has demonstrated that liver deficiency in Mfn1 mitochondrial protein in mice causes increased mitochondrial respiratory capacity and increased lipid consumption. Mfn1 KO mice are protected against insulin resistance induced by a high fat diet. In addition, under these conditions, liver deficiency of Mfn1 increased the abundance of the respiratory chain I complex, and mice showed increased sensitivity to treatment with the hypoglycemic compound metformin. These results suggest that inhibition of Mfn1 could improve glucose homeostasis in obese patients and increase the effectiveness of metformin (Kulkarni et al., Diabetes 2016).
In addition to these scientific contributions, our research team has obtained funding through 3 different proposals in 2016 (Plan Nacional Ministerio de Economía y Competitividad, Fundación Marató TV3, and Fundación Areces). Finally, we want to mention that our group has participated in a guide for the precise measurement of autophagic activity (Klionsky et al., 2016).
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