Modulation of mitochondrial morphology by bioenergetics defects in primary human fibroblasts.

Mitochondria are dynamic organelles with continuous fusion and fission, the equilibrium of which results in mitochondrial morphology. Evidence points to there being an intricate relationship between mitochondrial dynamics and oxidative phosphorylation. We investigated the bioenergetics modulation of mitochondrial morphology in five control cultured primary skin fibroblasts and seven with genetic alterations of oxidative phosphorylation. Under basal conditions, control fibroblasts had essentially filamentous mitochondria. Oxidative phosphorylation inhibition with drugs targeting complex I, III, IV or V induced partial but significant mitochondrial fragmentation, whereas dissipation of mitochondrial membrane potential (D Psi m) provoked complete fragmentation, and glycolysis inhibition had no effect. Oxidative phosphorylation defective fibroblasts had essentially normal filamentous mitochondria under basal conditions, although when challenged some of them presented with mild alteration of fission or fusion efficacy. Severely defective cells disclosed complete mitochondrial fragmentation under glycolysis inhibition. In conclusion, mitochondrial morphology is modulated by D Psi m but loosely linked to mitochondrial oxidative phosphorylation. Its alteration by glycolysis inhibition points to a severe oxidative phosphorylation defect.

[Organization and dynamics of the mitochondrial compartment]. / Organisation et dynamique du compartiment mitochondrial.

Mitochondria are essential organelles that are involved in numerous metabolic pathways and produce the major part of intracellular ATP by oxidative phosphorylation. Their ultrastructure was solved in the 1950s by electron microscopic analysis of ultrathin sections. Based on these pioneering studies and on the endosymbiotic origin of mitochondria, cells are often assumed to contain numerous independent mitochondria with a size similar to that of bacteria. However, electron microscopy of thick sections reveals that mitochondria form elongated and branched filaments. Optical microscopy of living cells demonstrates that mitochondrial filaments continuously modify their position and morphology and that they undergo frequent fission and fusion reactions. In this review, we revise the actual knowledge on the ultrastructure, the organization and the dynamics of the mitochondrial compartment. We review recent findings showing that mitochondria exchange molecules by fusion and we present the main proteins involved in mitochondrial fusion and fission reactions. Finally, we discuss the functional and physiological relevance of mitochondrial dynamics.