Mitochondrial functions infive casesofhuman neuromuscular disorders

SUMMARY We determined therespiration, respiratory control, andPi:Oratios withdifferent substrates inmitochondria isolated fromfive casesofhumanneuromuscular disorders (two cases ofcentral coredisease, twocasesofneuropathy ofDejerine-Sottas, andone caseofKugelbergWelander's disease) andcompared themwithnormal humanmuscle. Inallthemyopathies studied, a severederangement oftherespiratory control withvariable derangement ofoxidative phosphorylation wasfound. Thissupports theideathat agroupofneuromyopathies shares thesame biochemical lesion astheso-called mitochondrial myopathies, forming withthema groupofmyopathies which may berelated through asimilar biochemical lesion ofvarying degree. Alternatively, disturbance of mitochondrial functions ina numberofmyopathies couldbeconsidered asa non-specific finding. Despite thefrequent occurrence ofmorphological changes inmitochondria inmanytypes ofhumanneuromuscular disorders (Gruner, 1963; AleuandAfifi, 1964; Gonatas, Perez, Shy, andEvangelista, 1965; Norris andPanner, 1966; Gonatas, 1967; Engel andDale, 1968; Chou, 1969), several myopathies havebeendescribed inwhichabnormalities ofthis organelle were -considered tobeofmajorsignificance (Luft, Ikkos, Palmieri, Ernster, andAfzelius, 1962; Shy,Gonatas, Perez, 1966; Coleman, Nienhuis, Brown,Munsat, andPearson, 1967; VanWijngaarden, Bethlem, Meyer, Hiilsmann, andFeltkamp,1967; Price, Gordon, Munsat, andPearson,1967; Hulsmann, Bethlem, Meyer, Fleury, andSchellens, 1967; D'Agostino, Ziter, Rallison, andBray,1968;Bradley, Hudgson, GardnerMedwin, andWalton, 1969; Spiro, Prineas, and Moore,1970; Salomon, Esiri, andRuderman, 1971) andforsuchcases, theterm'mitochondrial myopathies' hasbeencoined (Price etal., 1967). Mitochondrial myopathies donotseemto