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Hernandez-Alvarez 2013 Antioxid Redox Signal

From Bioblast
Publications in the MiPMap
Hernández-Alvarez MI, Paz JC, Sebastián D, Muñoz JP, Liesa M, Segalés J, Palacín M, Zorzano A (2013) Glucocorticoid modulation of mitochondrial function in hepatoma cells requires the mitochondrial fission protein Drp1. Antioxid Redox Signal 19:366-78.

» PMID: 22703557 Open Access

Hernandez-Alvarez MI, Paz JC, Sebastian D, Munoz JP, Liesa M, Segales J, Palacin M, Zorzano A (2013) Antioxid Redox Signal

Abstract: Glucocorticoids, such as dexamethasone, enhance hepatic energy metabolism and gluconeogenesis partly through changes in mitochondrial function. Mitochondrial function is influenced by the balance between mitochondrial fusion and fission events. However, whether glucocorticoids modulate mitochondrial function through the regulation of mitochondrial dynamics is currently unknown.

Here, we report that the effects of dexamethasone on mitochondrial function and gluconeogenesis in hepatoma cells are dependent on the mitochondrial fission protein dynamin-related protein 1 (Drp1). Dexamethasone increased routine oxygen consumption, maximal respiratory capacity, superoxide anion, proton leak, and gluconeogenesis in hepatoma cells. Under these conditions, dexamethasone altered mitochondrial morphology, which was paralleled by a large increase in Drp1 expression, and reduced mitofusin 1 (Mfn1) and Mfn2. In vivo dexamethasone treatment also enhanced Drp1 expression in mouse liver. On the basis of these observations, we analyzed the dependence on the Drp1 function of dexamethasone effects on mitochondrial respiration and gluconeogenesis. We show that the increase in mitochondrial respiration and gluconeogenesis induced by dexamethasone are hampered by the inhibition of Drp1 function.

Our findings provide the first evidence that the effects of glucocorticoids on hepatic metabolism require the mitochondrial fission protein Drp1.

In summary, we demonstrate that the mitochondrial effects of dexamethasone both on mitochondrial respiration and on the gluconeogenic pathway depend on Drp1. Keywords: Mitochondrial dynamics, Dexasmethason, Gluconeogenesis, Mitofusin

O2k-Network Lab: ES Barcelona Zorzano A

Labels: MiParea: Respiration, mt-Structure;fission;fusion, Genetic knockout;overexpression 

Stress:Oxidative stress;RONS  Organism: Rat  Tissue;cell: Liver, Other cell lines  Preparation: Homogenate 

Coupling state: OXPHOS, ET  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k