MORPHOLOGY OF THE MITOCHONDRIA IN HEAT-SHOCK-PROTEIN-60 DEFICIENT FIBROBLASTS FROM MITOCHONDRIAL MYOPATHY PATIENTS - EFFECTS OF STRESS CONDITIONS

We have described two mitochondrial (mt) myopathy patients with reduce d activities of various mt enzymes associated with significantly decre ased amounts of heat shock protein 60 (hsp60). Experimental evidence s uggested that the lack of hsp60 was the primary defect. Since hsp60 is essential for the proper folding of enzyme subunits in the mt matrix a partial deficiency of this protein can explain the observed defects of the mitochondria. Here we report on morphological studies aimed at obtaining more insight into the relation between lack of hsp60 and pat hological changes of the mitochondria. Under standard culture conditio ns mitochondria in the partially hsp60 deficient fibroblasts showed pr ofound morphological aberrations. In contrast, the mitochondria in fib roblasts from a MELAS patient and a cytochrome c oxidase-deficient pat ient appeared normal. Under stress conditions the integrity of the hsp 60 deficient mitochondria declined even further: heat shock induced a temporary collapse of the electrochemical potential across the inner m t membrane, but did not affect the ultrastructure of the mitochondria; prolonged growth in confluent cultures resulted in decrease in mt num ber. The altered mt morphology in the hsp60 deficient cells is probabl y indicative of the severely impaired mt metabolism whereas the decrea sed stress tolerance is likely to be a direct result of paucity of the heat shock protein. Both variables are potentially useful in the diag nosis and molecular characterization of mt disorders with systemic man ifestation and multiple enzyme deficiency.