EXPRESSION OF OXIDATIVE-PHOSPHORYLATION GENES IN MUSCLE-CELL CULTURESFROM PATIENTS WITH MITOCHONDRIAL MYOPATHIES

The expression of several mitochondrial and nuclear genes involved in ATF production was examined in cells cultured from muscle biopsies of patients harboring mitochondrial pathologies. The transcript patterns in muscle cells from the patients affected by carnitine palmitoyl tran sferase II or 2-ketoglutarate dehydrogenase deficiencies were almost s imilar to control patterns. In the opposite, patterns were strikingly abnormal in all the other cell cultures from patients with defects in enzymatic complexes involved in oxidative phosphorylation: mitochondri al complex II and III deficiencies, two MELAS syndromes (myopathy, enc ephalopathy, lactic acidosis and stroke like episodes), a case of Kear ns-Sayre syndrome and a case of chronic progressive external ophthalmo plegia. In cultured muscle cells from patients with mtDNA mutations, t he percentage of mutated mtDNA was low as compared with those determin ed in the corresponding skeletal muscle biopsy. Moreover, the complex II defect resulting of a nuclear mutation was not expressed in the cel l cultures. Thus, an undetermined transcriptional event, transmitted f rom muscle biopsies to cultured muscle cells, should be involved to ac count for such abnormal transcript patterns.