In the present work, we demonstrate the possibility of using human blood platelets as mitochondrial donors for the repopulation of
mtDNA-less (rho 0) cells. The noninvasive nature of platelet isolation, combined with the prolonged viability of platelet mitochondria and the simplicity and efficiency of the mitochondria-transfer procedure, has substantially increased the applicability of the rho 0 cell transformation approach for mitochondrial genetic analysis and for the study of
mtDNA-linked diseases. This approach has been applied to platelets from several normal human individuals and one individual affected by the
myoclonic-epilepsy-and-ragged-red-fibers (
MERRF) encephalomyopathy. A certain variability in respiratory capacity was observed among the platelet-derived rho 0 cell transformants from a given normal subject, and it was shown to be unrelated to their
mtDNA content. The results of sequential transfer of mitochondria from selected transformants into a rho 0 cell line different from the first rho 0 acceptor strongly suggest that this variability reflected, at least in part, differences in nuclear gene content and/or activity among the original recipient cells. A much greater variability in respiratory capacity was observed among the transformants derived from the
MERRF patient and was found to be related to the presence and amount of the mitochondrial
tRNALys mutation associated with the
MERRF syndrome. An analysis of the relationship between proportion of
mtDNA carrying the
MERRF mutation and degree of respiratory activity in various transformants derived from the
MERRF patient revealed an unusual complementation behavior of the
tRNALys mutation, possibly reflecting the distribution of mutant
mtDNA among the platelet mitochondria.