Understanding the pathobiology of mitochond rial (nit) I)NA diseases involw,s not only eharacterisation of the elleeLs of individual mutations on respiratory function, a well explored area, but also elucidation of the changes in t)olh the load and distribution of mutant mIDNA (energy mosaicism) over serial ceil generations. In this study, we explore the relationship between nit gemtype and phenotype in vitro in skelelal myoblasts derived from mt cytopathy patients with a high mutant load (MELAS rt 3243 A to C, rnutatiozl and CPEO ,i.9 kb common deletion) and grown to exhaustion. A progressiw increase in cell doubling time with growth exhaustion was found in all cell lines. In cytopathy-derived myoblasts, a progressive elimination of mutant mIDNA genomes was observed together with an improvement in respiratory chain activity. In control myoblast, a small deterioration in respiratory activity was seen in late cultures and was accompanied by depressed synthesis of certain mitochondrially encoded sul)unils.
|Publication status||Published - 1 Dec 1997|