Selective actions of mitochondrial fission/fusion genes on metabolism-secretion coupling in insulin-releasing cells
| Autor: | Yves Benoît Mattenberger, Kyu Sang Park, Piero Marchetti, Andreas Wiederkehr, Jean-Claude Martinou, Clare L. Kirkpatrick, Nicolas Demaurex, Claes B. Wollheim |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Mitochondrion
ddc:616.07 Biochemistry Mitochondrial apoptosis-induced channel Membrane Fusion Mitochondrial Membrane Transport Proteins GTP Phosphohydrolases Adenosine Triphosphate Insulin-Secreting Cells Insulin Secretion MFN1 Exocytosis/physiology Insulin biology Mitochondrial Proteins/genetics/metabolism Membrane Proteins/genetics/metabolism Insulin/genetics/secretion Cell biology Mitochondria Metabolism and Bioenergetics Insulin-Secreting Cells/cytology/metabolism Mitochondrial fission ATP–ADP translocase Signal Transduction Adenosine Triphosphate/genetics/metabolism Exocytosis Mitochondrial Proteins Mitochondrial membrane transport protein Cell Line Tumor Animals Humans Glucose/genetics/metabolism Secretory Vesicles/genetics/metabolism Membrane Transport Proteins/genetics/metabolism Rats Wistar ddc:612 Molecular Biology Mitochondria/genetics/metabolism GTP Phosphohydrolases/genetics/metabolism Signal Transduction/physiology Secretory Vesicles Membrane Proteins Membrane Transport Proteins Cell Biology Rats Cytosol Glucose Mitochondrial permeability transition pore biology.protein Membrane Fusion/physiology |
| Zdroj: | Journal of Biological Chemistry, Vol. 283, No 48 (2008) pp. 33347-56 |
| ISSN: | 0021-9258 |
| Popis: | Mitochondria form filamentous networks that undergo continuous fission/fusion. In the pancreatic β-cells, mitochondria are essential for the transduction of signals linking nutrient metabolism to insulin granule exocytosis. Here we have studied mitochondrial networks in the insulinoma cell line INS-1E, primary rat and human β-cells. We have further investigated the impact of mitochondrial fission/fusion on metabolism-secretion coupling in INS-1E cells. Overexpression of hFis1 caused dramatic mitochondrial fragmentation, whereas Mfn1 evoked hyperfusion and the aggregation of mitochondria. Cells overexpressing hFis1 or Mfn1 showed reduced mitochondrial volume, lowered cellular ATP levels, and as a consequence, impaired glucose-stimulated insulin secretion. Decreased mitochondrial ATP generation was partially compensated for by enhanced glycolysis as indicated by increased lactate production in these cells. Dominant-negative Mfn1 elicited mitochondrial shortening and fragmentation of INS-1E cell mitochondria, similar to hFis1. However, the mitochondrial volume, cytosolic ATP levels, and glucose-stimulated insulin secretion were little affected. We conclude that mitochondrial fragmentation per se does not impair metabolism-secretion coupling. Through their impact on mitochondrial bioenergetics and distribution, hFis1 and Mfn1 activities influence mitochondrial signal generation thereby insulin exocytosis. |
| Databáze: | OpenAIRE |
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