Abnormal levels of human mitochondrial transcription factor A in skeletal muscle in mitochondrial encephalomyopathies

Human mitochondrial transcription factor A (h-mtTFA or Tfam), a 25-kDa protein encoded by a nuclear gene located on chromosome 10q21, is involved in the control of replication and transcription of mtDNA. To better understand the complex relationship between h-mtTFA and mitochondrial function, we assessed by western blot the levels of h-mtTFA in skeletal muscle from 7 patients affected by mitochondrial diseases (MD) caused by different mtDNA mutations. We related these results to exercise lactate production as well as to the pathologic features of the underlying myopathy. h-mtTFFA levels were significantly inversely related to blood lactate and the percent of RRF, borderline to cox negative fibers. Our results indicate that h-mtTFA may be involved in the cascade of events which determine functional impairment of MD.