EXPRESSION OF CYTOCHROME-C-OXIDASE SUBUNITS ENCODED BY MITOCHONDRIAL OR NUCLEAR-DNA IN THE MUSCLE OF PATIENTS WITH ZIDOVUDINE MYOPATHY

The present study was carried out to determine whether a selective dec rease of mitochondrial (mt) DNA-encoded cytochrome c oxidase (CCO) sub units occurs in zidovudine myopathy, as expected with a compound known to induce selective mtDNA depletion. Fourteen HIV-infected patients w ith zidovudine myopathy were studied. Thirteen had partial CCO deficie ncy assessed by histochemistry. Western blot analysis of CCO subunits (II/III, IV, Va, Vb, VIa, VIb, VIc, VIIa, VIIb, and VIIc) was performe d on muscle biopsy samples. We evaluated the mtDNA-encoded subunits to nuclear DNA-encoded subunits ratio with the II/III to IV ratio. Patie nts had either a selective decrease of mtDNA-encoded CCO subunits (3 p atients), or an overall decrease affecting both mtDNA-and nuclear DNA- encoded subunits (5 patients), or a normal expression of CCO subunits (6 patients). Positive correlations could not be established between t he pattern of expression of CCO subunits and total zidovudine intake, degree of inflammation, and percentages of ragged-red fibers or CCO-de ficient fibers. The finding of a decrease of both mtDNA- and nuclear D NA-encoded CCO subunits suggests that a factor additional to zidovudin e could be implicated in the pathogenesis of the myopathy, at least in some patients. New insights into the pathogenesis of zidovudine myopa thy might come from the use of more sensitive methods, including evalu ation of CCO subunits in single fibers.