Mitochondrial fragmentation impairs insulin-dependent glucose uptake by modulating Akt activity through mitochondrial Ca2+ uptake

Andrea del Campo, Valentina Parra, César Vásquez-Trincado, Tomás Gutiérrez, Pablo E. Morales, Camila López-Crisosto, Roberto Bravo-Sagua, Mario F. Navarro-Marquez, Hugo E. Verdejo, Ariel Contreras-Ferrat, Rodrigo Troncoso, Mario Chiong, Sergio Lavandero

Resultado de la investigación: Article

32 Citas (Scopus)

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.

Idioma originalEnglish
Páginas (desde-hasta)E1-E13
PublicaciónAmerican Journal of Physiology - Endocrinology and Metabolism
Volumen306
N.º1
DOI
EstadoPublished - 1 ene 2014
Publicado de forma externa

Huella dactilar

Insulin
Glucose
Muscle Cells
Mitochondrial Dynamics
Skeletal Muscle
Ruthenium Red
Mitochondrial Proteins
Respiratory Rate
Organelles
Mitochondria
Phosphorylation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Citar esto

del Campo, Andrea ; Parra, Valentina ; Vásquez-Trincado, César ; Gutiérrez, Tomás ; Morales, Pablo E. ; López-Crisosto, Camila ; Bravo-Sagua, Roberto ; Navarro-Marquez, Mario F. ; Verdejo, Hugo E. ; Contreras-Ferrat, Ariel ; Troncoso, Rodrigo ; Chiong, Mario ; Lavandero, Sergio. / Mitochondrial fragmentation impairs insulin-dependent glucose uptake by modulating Akt activity through mitochondrial Ca2+ uptake. En: American Journal of Physiology - Endocrinology and Metabolism. 2014 ; Vol. 306, N.º 1. pp. E1-E13.
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title = "Mitochondrial fragmentation impairs insulin-dependent glucose uptake by modulating Akt activity through mitochondrial Ca2+ uptake",
abstract = "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.",
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del Campo, A, Parra, V, Vásquez-Trincado, C, Gutiérrez, T, Morales, PE, López-Crisosto, C, Bravo-Sagua, R, Navarro-Marquez, MF, Verdejo, HE, Contreras-Ferrat, A, Troncoso, R, Chiong, M & Lavandero, S 2014, 'Mitochondrial fragmentation impairs insulin-dependent glucose uptake by modulating Akt activity through mitochondrial Ca2+ uptake', American Journal of Physiology - Endocrinology and Metabolism, vol. 306, n.º 1, pp. E1-E13. https://doi.org/10.1152/ajpendo.00146.2013

Mitochondrial fragmentation impairs insulin-dependent glucose uptake by modulating Akt activity through mitochondrial Ca2+ uptake. / del Campo, Andrea; Parra, Valentina; Vásquez-Trincado, César; Gutiérrez, Tomás; Morales, Pablo E.; López-Crisosto, Camila; Bravo-Sagua, Roberto; Navarro-Marquez, Mario F.; Verdejo, Hugo E.; Contreras-Ferrat, Ariel; Troncoso, Rodrigo; Chiong, Mario; Lavandero, Sergio.

En: American Journal of Physiology - Endocrinology and Metabolism, Vol. 306, N.º 1, 01.01.2014, p. E1-E13.

Resultado de la investigación: Article

TY - JOUR

T1 - Mitochondrial fragmentation impairs insulin-dependent glucose uptake by modulating Akt activity through mitochondrial Ca2+ uptake

AU - del Campo, Andrea

AU - Parra, Valentina

AU - Vásquez-Trincado, César

AU - Gutiérrez, Tomás

AU - Morales, Pablo E.

AU - López-Crisosto, Camila

AU - Bravo-Sagua, Roberto

AU - Navarro-Marquez, Mario F.

AU - Verdejo, Hugo E.

AU - Contreras-Ferrat, Ariel

AU - Troncoso, Rodrigo

AU - Chiong, Mario

AU - Lavandero, Sergio

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

KW - Calcium

KW - Insulin

KW - Mfn2

KW - Mitochondrial fragmentation

KW - Opa1

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U2 - 10.1152/ajpendo.00146.2013

DO - 10.1152/ajpendo.00146.2013

M3 - Article

AN - SCOPUS:84891522787

VL - 306

SP - E1-E13

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 0193-1849

IS - 1

ER -