Article

Mobilization of adenine nucleotide translocators as molecular bases of the biochemical threshold effect observed in mitochondrial diseases.

INSERM, Université Victor Segalen-Bordeaux 2, 146 rue Léo-Saignat, F-33076 Bordeaux Cedex, France.
Journal of Biological Chemistry (impact factor: 4.77). 06/2004; 279(19):20411-21. DOI:10.1074/jbc.M314259200 pp.20411-21
Source: PubMed

ABSTRACT The existence of a biochemical threshold effect in the metabolic expression of oxidative phosphorylation deficiencies has considerable implications for the understanding of mitochondrial bioenergetics and the study of mitochondrial diseases. However, the molecular bases of this phenomenon remain unclear. We report here a new mechanism to explain this threshold effect, based on a reserve of enzymes not initially participating in the respiratory rate that can be activated either to respond to a flux increase or to compensate for a defect induced by a mutation. We show that this mobilization occurs through 1) the assembly of inactive adenine nucleotide translocator isoform 1 subunits into oligomeric active carriers or 2) conformational changes in the adenine nucleotide translocator isoform 1 in a permeability transition pore-like structure. We discuss how these transitions are sensitive to the steady state of oxidative phosphorylation functioning or tissue and analyze their consequences on the threshold effect.

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Keywords

adenine nucleotide translocator isoform 1
 
biochemical threshold effect
 
consequences
 
inactive adenine nucleotide translocator isoform 1 subunits
 
metabolic expression
 
mitochondrial diseases
 
oligomeric active carriers
 
oxidative phosphorylation
 
oxidative phosphorylation deficiencies
 
respiratory rate
 
steady state
 
threshold effect
 
transitions