MITOCHONDRIAL MOBILITY IN DIFFERENTIATING MUSCLE HETEROKARYONS

Ragged-red fibers, a morphological hallmark of many patients with mito chondrial encephalomyopathies who harbor mitochondrial DNA (mtDNA) mut ations, usually contain varying ratios of mutated and wild-type mtDNAs . Deficient respiratory function in muscle is almost invariably segmen tal. To investigate whether this observation may be explained by restr icted lateral movement of mitochondria within myofibers, we studied th e spatial and temporal behavior of two different mitochondrial populat ions within multinucleate myotubes. We co-cultured normal human and mo use myoblasts, allowed them to fuse into muscle heterokaryons and inve stigated whether the mitochondria remained segregated, or migrated and intermixed. Human and mouse nuclei were identified by their different ial staining pattern with the dye Hoechst 33 258 and mitochondria were distinguished immunologically and by in situ hybridization. Although we observed some territoriality at very early time points after myobla st fusion, there was rapid intermixing of the mitochondrial population s, as early as 48 h after myoblast fusion. We conclude that mitochondr ia, unlike many other muscle components, lack territorial organization in cultured, differentiating heterokaryons. (C) 1997 Elsevier Science B.V.