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First published online 13 February 2007
doi: 10.1242/jcs.03381


Journal of Cell Science 120, 838-848 (2007)
Published by The Company of Biologists 2007
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Research Article

Mitochondrial bioenergetics and structural network organization

Giovanni Benard1, Nadège Bellance1, Dominic James2, Philippe Parrone2, Helder Fernandez3, Thierry Letellier1 and Rodrigue Rossignol1,*

1 Institut National de la Santé et de la Recherche Médicale (INSERM), U688 Physiopathologie Mitochondriale, Universite Victor Segalen-Bordeaux 2, 146 rue Leo-Saignat, F-33076 Bordeaux cedex, France
2 Department of Cell Biology, University of Geneva, 30, Quai Ansermet 1211 Geneva 4, Switzerland
3 Laboratoire de Biologie Moleculaire et de Sequencage, Institut de Biochimie et Genetique Cellulaires, UMR Universite Victor Segalen Bordeaux 2-CNRS 5095, box 64, 146 rue Leo Saignat, F-33076 Bordeaux Cedex, France

* Author for correspondence (e-mail: rossig{at}u-bordeaux2.fr)

Accepted 13 December 2006

Mitochondria form a dynamic network, and it remains unclear how the alternate configurations interact with bioenergetics properties. The metabolic signals that link mitochondrial structure to its functional states have not been fully characterized. In this report, we analyze the bidirectional relationships between mitochondrial morphology and function in living human cells. First, we determined the effect of mitochondrial fission on energy production by using small interfering RNA (siRNA) targeting DRP1, which revealed the importance of membrane fluidity on the control of bioenergetics. Second, we followed the effect of rotenone, a specific inhibitor of respiratory chain complex I, which causes large structural perturbations, once a threshold was reached. Last, we followed changes in the mitochondrial network configuration in human cells that had been treated with modulators of oxidative phosphorylation, and in fibroblasts from two patients with mitochondrial disease where the respiratory rate, {Delta}{Psi} and the generation of reactive oxygen species (ROS) were measured. Our data demonstrate that the relationship between mitochondrial network organization and bioenergetics is bidirectional, and we provide a model for analyzing the metabolic signals involved in this crosstalk.

Key words: Mitochondrial network, Fission, DRP1, Oxidative phosphorylation, Threshold effect


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