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 prot ein encoded by a nuclear gene located on chromosome 10q21, is involved in t he control of replication and transcription of mtDNA. To better understand the complex relationship between h-mtTFA and mitochondrial function, we ass essed by western blot the levels of h-mtTFA in skeletal muscle from 7 patie nts affected by mitochondrial diseases (MD) caused by different mtDNA mutat ions. We related these results to exercise lactate production as well as to the pathologic features of the underlying myopathy. h-mtTFA levels were si gnificantly inversely related to blood lactate and the percent of RRF, bord erline to cox negative fibers. Our results indicate that h-mtTFA may be inv olved in the cascade of events which determine functional impairment of MD.