Mitochondrial mobility in differentiating muscle heterokaryons.
Ragged-red fibers, a morphological hallmark of many patients with mitochondrial encephalomyopathies who harbor mitochondrial DNA (mtDNA) mutations, usually contain varying ratios of mutated and wild-type mtDNAs. Deficient respiratory function in muscle is almost invariably segmental. To investigate whether this observation may be explained by restricted lateral movement of mitochondria within myofibers, we studied the spatial and temporal behavior of two different mitochondrial populations within multinucleate myotubes. We co-cultured normal human and mouse myoblasts, allowed them to fuse into muscle heterokaryons and investigated whether the mitochondria remained segregated, or migrated and intermixed. Human and mouse nuclei were identified by their differential 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 myoblast fusion, there was rapid intermixing of the mitochondrial populations, as early as 48 h after myoblast fusion. We conclude that mitochondria, unlike many other muscle components, lack territorial organization in cultured, differentiating heterokaryons.
Walker
U A
UA
Department of Neurology, Columbia University, College of Physicians and Surgeons, NY 10032, USA.
Walker
W F
WF
Miranda
A F
AF
D000818:Animals; D002459:Cell Fusion; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008870:Microtubules / Q000648:ultrastructure; D008931:Mitochondria, Muscle / Q000502:physiology*; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000473:pathology / Q000648:ultrastructure*; D011092:Polyethylene Glycols / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology
D004272:DNA, Mitochondrial; D013501:Surface-Active Agents; D011092:Polyethylene Glycols