Artículos de revistas
Mitochondrial fragmentation impairs insulin-dependent glucose uptake by modulating Akt activity through mitochondrial Ca2+ uptake
Fecha
2014Registro en:
Am J Physiol Endocrinol Metab 306: E1–E13, 2014
doi:10.1152/ajpendo.00146.2013
Autor
Del Campo Sfeir, Andrea Estefanía
Parra Ortíz, María 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 Cotal, 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 that control of mitochondrial
Ca2 uptake by mitochondrial morphology is a key event for insulininduced
glucose uptake.