Artículo de revista
Mitochondrial fragmentation impairs insulin-dependent glucose uptake by modulating Akt activity through mitochondrial Ca2+ uptake
Fecha
2014Registro en:
American Journal of Physiology - Endocrinology and Metabolism, Volumen 306, Issue 1, 2018,
01931849
15221555
10.1152/ajpendo.00146.2013
Autor
Del Campo, Andrea
Parra, Valentina
Vásquez Trincado, César Alonso
Gutiérrez, Tomás
Morales, Pablo E.
López Crisosto, Camila
Bravo Sagua, Roberto
Navarro Márquez, Mario F.
Verdejo, Hugo E.
Contreras Ferrat, Ariel Eduardo
Troncoso, Rodrigo
Chiong Lay, Mario
Lavandero González, Sergio
Institución
Resumen
Insulin is a major regulator of glucose metabolism, stimulating its mitochondrial oxidation in skeletal muscle cells. Mitochondria are dynamic organelles that can undergo structural remodeling in order to cope with these everchanging metabolic demands. However, the process by which mitochondrial morphology impacts insulin signaling in the skeletal muscle cells remains uncertain. To address this question, we silenced the mitochondrial fusion proteins Mfn2 and Opa1 and assessed insulin-dependent responses in L6 rat skeletal muscle cells. We found that mitochondrial fragmentation attenuates insulin-stimulated Akt phosphorylation, glucose uptake and cell respiratory rate. Importantly, we found that insulin induces a transient rise in mitochondrial Ca2+ uptake, which was attenuated by silencing Opa1 or Mfn2. Moreover, treatment with Ruthenium red, an inhibitor of mitochondrial Ca2+ uptake, impairs Akt signaling without affecting mitochondrial dynamics. All together, these results suggest th