PRIMARY AND SECONDARY DEFICIENCIES OF THE MITOCHONDRIAL RESPIRATORY CHAIN

The first observation of mitochondrial respiratory chain dysfunction was made in 1959 with the report of a biochemical defect in the skeletal muscle of a euthyroid patient with hypermetabolism. Since then, numerous disorders have been found to be associated with mitochondrial respiratory chain dysfunction, the nervous system being particularly affected. In 1988, the discovery of large-scale deletions of mitochondrial DNA (mtDNA) in mitochondrial myopathies and a point mutation associated with Leber's hereditary optic neuropathy marked the beginning of a new era of mitochondrial research with the identification of many more pathogenic mutations. More recently, there has been great interest in the role of mitochondrial dysfunction in neurodegenerative diseases and aging. In this review, we discuss inborn and acquired mitochondrial abnormalities and the relationship of mitochondrial respiratory chain dysfunction to neurological disorders.