On the pathogenesis of mitochondrial myopathies

Summary The intra-arterial injection of 2–4 dinitrophenol, an uncoupler of oxidative phosphorylation, resulted in the production of ragged red fibers.The ultrastructure of these fibers showed intramitochondrial paracrystalline inclusions, laminar and fingerprint bodies. Antimycin A and oligomycin injection (which inhibit mitochondrial respiration) only caused swelling and disruption of the mitochondria. An increase in muscle lactic acid, decrease in ATP, glycogen and phosphocreatine was observed after the injection of all these agents. This indicates that lactic acidosis has no significant role in the pathogenesis of mitochondrial pathology. It is concluded that mitochondrial changes are a morphological expression of uncopuled but intact mitochondrial respiration.