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Scientific article
English

Selective actions of mitochondrial fission/fusion genes on metabolism-secretion coupling in insulin-releasing cells

Published inThe Journal of biological chemistry, vol. 283, no. 48, p. 33347-33356
Publication date2008
Abstract

Mitochondria form filamentous networks that undergo continuous fission/fusion. In the pancreatic beta-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 beta-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.

Keywords
  • Adenosine Triphosphate/genetics/metabolism
  • Animals
  • Cell Line, Tumor
  • Exocytosis/physiology
  • GTP Phosphohydrolases/genetics/metabolism
  • Glucose/genetics/metabolism
  • Humans
  • Insulin/genetics/secretion
  • Insulin-Secreting Cells/cytology/metabolism
  • Membrane Fusion/physiology
  • Membrane Proteins/genetics/metabolism
  • Membrane Transport Proteins/genetics/metabolism
  • Mitochondria/genetics/metabolism
  • Mitochondrial Proteins/genetics/metabolism
  • Rats
  • Rats, Wistar
  • Secretory Vesicles/genetics/metabolism
  • Signal Transduction/physiology
Citation (ISO format)
PARK, Kyu-Sang et al. Selective actions of mitochondrial fission/fusion genes on metabolism-secretion coupling in insulin-releasing cells. In: The Journal of biological chemistry, 2008, vol. 283, n° 48, p. 33347–33356. doi: 10.1074/jbc.M806251200
Main files (1)
Article (Accepted version)
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Identifiers
ISSN of the journal0021-9258
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