title: Mitochondrial threshold effects.
abstract: The study of mitochondrial diseases has revealed dramatic variability in the phenotypic presentation of mitochondrial genetic defects. To attempt to understand this variability, different authors have studied energy metabolism in transmitochondrial cell lines carrying different proportions of various pathogenic mutations in their mitochondrial DNA. The same kinds of experiments have been performed on isolated mitochondria and on tissue biopsies taken from patients with mitochondrial diseases. The results have shown that, in most cases, phenotypic manifestation of the genetic defect occurs only when a threshold level is exceeded, and this phenomenon has been named the 'phenotypic threshold effect'. Subsequently, several authors showed that it was possible to inhibit considerably the activity of a respiratory chain complex, up to a critical value, without affecting the rate of mitochondrial respiration or ATP synthesis. This phenomenon was called the 'biochemical threshold effect'. More recently, quantitative analysis of the effects of various mutations in mitochondrial DNA on the rate of mitochondrial protein synthesis has revealed the existence of a 'translational threshold effect'. In this review these different mitochondrial threshold effects are discussed, along with their molecular bases and the roles that they play in the presentation of mitochondrial diseases.
authors.affiliation: INSERM-EMI 9929, Physiologie mitochondriale, Université Victor Segalen-Bordeaux 2, 146 rue Léo-Saignat, F-33076 Bordeaux-cedex, France. rossig@u-bordeaux2.fr
authors.forename: Rodrigue
authors.initials: R
authors.lastname: Rossignol
authors.forename: Benjamin
authors.initials: B
authors.lastname: Faustin
authors.forename: Christophe
authors.initials: C
authors.lastname: Rocher
authors.forename: Monique
authors.initials: M
authors.lastname: Malgat
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Mazat
authors.forename: Thierry
authors.initials: T
authors.lastname: Letellier
mesh_terms: D000818:Animals; D002460:Cell Line; D004272:DNA, Mitochondrial; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D010085:Oxidative Phosphorylation; D010641:Phenotype
chemical_list: D004272:DNA, Mitochondrial