[Evolution of the concept of mitochondrial disease]

The concept of mitochondrial disease originated in 1962 when Luft and co-workers described a patient with non thyroidal hypermetabolism related to loose coupling of oxidation-phosphorylation in muscle mitochondria. Over the following quarter of century, with the routine use of the Engel-Gomory staining on muscle biopsy revealing ragged-red fibres as a convenient markers for mitochondrial pathology, numerous papers described clinical, biochemical and morphological aspects of mitochondrial encephalomyopathies. With the discovery in 1988 of mutations in mitochondrial DNA, the concept of mitochondrial disease with maternal transmission led to an explosive expansion of research in the field. Throughout the 1990's the rapid identification of multiple mitochondrial gene defects associated with clinically diverse disorders has left practitioners puzzled about diagnosing such heterogeneous and complexes syndromes. The great complexity of the system and the ubiquitous repartition of mitochondria explain the wide variety of clinical phenotypes associated with primary mitochondrial diseases due to mutations in the mitochondrial genome, in the nuclear genome or in the cross-talk between the two genomes and regulations. In the past few years, the pivotal role of mitochondria in drug sensitivity, their key role in aging, apoptosis or neurodegeneration lead to a mitochondial medicine. Here the term of mitochondrial disease is limited to genetic defect in the respiratory chain where advance were recently especially significant for the evolution of the concept and updated classification.