Myopathies cytochrome oxidase

The condition known as fatal infantile mitochondrial myopathy and renal dysfunction involves severe diminution or absence of most oxidoreductases of the respiratory chain. MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke) is an inherited condition due to NADHiubiquinone oxidoreductase (complex I) or cytochrome oxidase deficiency. It is caused by a muta-... 

Myopathies have been described in several sporadic cases with lactic acidosis, cytochrome oxidase (COX)-positive RRF in muscle, and isolated complex I deficiency, and have been attributed to various pathogenic mutations in ND genes. The sporadic nature of these myopathies suggests that the ND mutations are de novo, arising spontaneously in myogenic stem cells after germ-layer differentiation (somatic mutations) [14]. 

M19. Miiller-Hocker, J., Johannes, A., Droste, M., Kadenbach, B., Pongratz, D., and Hubner, G., Fatal mitochondrial myopathy in Kearns-Sayre syndrome with deficiency of cytochrome oxidase in the cardiac and skeletal muscle An enzyme-histochemical ultra-immunocytochemical fine structural study in longterm frozen autopsy tissue. Virchows Arch. B Cell Pathol. Incl. Mol. Pathol. 52, 353-367 (1986). 

In contrast with the fall in the activity of muscle glycolytic enzymes in human muscular dystrophy, Dreyfus and his colleagues (DIO) found little or no decrease in the concentrations of certain enzymes involved in oxidative breakdown of fuel, notably succinate dehydrogenase, cytochrome oxidase, fumarase, and aconitase. In the mouse myopathy, the concentration of cytochrome oxidase is increased (W12) elevated levels of respiratory enzymes have been reported also in myopathy resulting from vitamin E deficiency (D6) and in genetically dystrophic chickens... 

In vivo, patients treated with AZT develop a mitochondrial myopathy with mitochondrial DNA depletion, deficiency of cytochrome c oxidase (complex IV), intracellular fat accumulation, high lactate production and marked phosphocreatine depletion (Lewis and Dalakas 1995 Dalakas 2001). Clinically, the patient presents with fatigue, myalgia, muscle weakness, wasting and elevated serum creatine kinase. Muscle biopsy shows ragged red fibers , the characteristic histopathologic changes of mitochondrial myopathy, cansed by subsarcolemmal accumulation of mitochondria (Lewis and Dalakas 1995). 

Diaz, F., Thomas, C. K., Garcia, S., Hernandez, D. and Moraes, C. T. (2005) Mice lacking COXIO in skeletal muscle recapitulate the phenotype of progressive mitochondrial myopathies associated with cytochrome c oxidase deficiency. Hum Mol Genet 14, 2737-2748. 

Although DNA mutations in nuclear DNA may cause mitochondrial dysfunction, the majority of genetically defined mitochondrial diseases are caused by mutations in mtDNA (M15, PI, S4). Point mutations and deletions of mtDNA have been reported to be associated with or responsible for mitochondrial myopathies and/or encephalomyopathies (M15, PI, S4). Patients with such diseases usually manifest major clinical symptoms early in life and at a later stage may develop additional multisystem disorders such as encephalopathy and/or peripheral neuropathy. Most of the mitochondrial myopathies occur sporadically and are often caused by large-scale mtDNA deletions (PI). However, there are several reports on maternally inherited mitochondrial myopathy and familial mitochondrial myopathy. These patients usually harbor a specific mtDNA mutation and often exhibit defects in NADH-CoQ reductase and/or cytochrome c oxidase. 

Yang, Z.P., Dettham, W-D. (1998). Lipid peroxidation and changes of cytochrome c oxidase and xanthine oxidase in organophosphoms anticholinesterase-induced myopathy. J. Physiol. (Paris) 92 157-61. 

Chabrol B, Mancini J, Chretien D, Rustin P, Munnich A, Pinsard N (1994) Valproate-induced hepatic failure in a case of cytochrome c oxidase deficiency. Eur J Pediatr 153 133-135 Chariot P, Drogou I, de Lacroix-Szmania I, Ehezer-Vanerot MC, Chazaud B, Lombes A, Schaeffer A, Zafrani ES (2000) Zidovudine-indueed mitochondrial disorder with massive liver steatosis, myopathy, lactic acidosis, and mitochondrial DNA depletion. J Hepatol 32 364-365 Chen CH, Cheng YC (1989) Delayed cytotoxicity and selective loss of mitochondrial DNA in cells treated with the anti-human immunodeflcieney vims compound 2, 3 -dideoxycytidine. J Biol Chem 264 11934-11937... 

Respiratory-chain disorders (with mitochondrial myopathy) Lactic Various, including cytochromes b, aa, cytochrome c oxidase, NADH-coenzyme Q reductase 15.6... 

Deficient activity of muscle cytochrome c oxidase has also been reported in a patient with a mitochondrial myopathy associated with chronic lactic acidaemia, growth failure and nerve deafness (Monnens etaL, 1975) and in a patient with subacute necrotizing encephalomyelopathy (Leigh s disease)... 

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