Glucocorticoid Modulation of Mitochondrial Function in Hepatoma Cells Requires the Mitochondrial Fission Protein Drp1
| Autor: | Antonio Zorzano, Jessica Segalés, José C. Paz, Juan Pablo Muñoz, David Sebastián, Manuel Palacín, Marc Liesa, María Isabel Hernández-Alvarez |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Dynamins
endocrine system medicine.medical_specialty Carcinoma Hepatocellular Physiology Blotting Western Clinical Biochemistry MFN2 Biology Biochemistry Dexamethasone Cell Line Mice 03 medical and health sciences chemistry.chemical_compound Oxygen Consumption 0302 clinical medicine Superoxides Internal medicine medicine Animals MFN1 Forum Original Research CommunicationsMitochondrial Fission And Fusion (A. Zorzano Ed.) Glucocorticoids Molecular Biology 030304 developmental biology General Environmental Science 0303 health sciences Superoxide Gluconeogenesis Hydrogen Peroxide Cell Biology Mitochondria Rats Endocrinology Liver chemistry mitochondrial fusion General Earth and Planetary Sciences Mitochondrial fission 030217 neurology & neurosurgery Glucocorticoid medicine.drug |
| Zdroj: | Antioxidants & Redox Signaling; Vol 19 |
| ISSN: | 1523-0864 |
| DOI: | 10.1089/ars.2011.4269 |
| Popis: | Aims: 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. Results: 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. Innovation: Our findings provide the first evidence that the effects of glucocorticoids on hepatic metabolism require the mitochondrial fission protein Drp1. Conclusion: In summary, we demonstrate that the mitochondrial effects of dexamethasone both on mitochondrial respiration and on the gluconeogenic pathway depend on Drp1. Antioxid. Redox Signal. 19, 366–378. |
| Databáze: | OpenAIRE |
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