Mitochondrial protein content and in vivo synthesis rates in skeletal muscle from critically ill rats.
1. Recently we reported decreased activities of two mitochondrial marker enzymes (citrate synthase and cytochrome c oxidase) in skeletal muscle from a rat model of critical illness (zymosan injection). In the present study we investigated (i) whether these decreases in enzyme activity reflect a reduction in mitochondrial content and (ii) whether this potential reduction in mitochondrial content was the result of decreased mitochondrial protein synthesis rates. 2. Mitochondrial protein content was calculated from the activities of cytochrome c oxidase in whole-muscle homogenates and purified mitochondria. Synthesis rates of mitochondrial protein in vivo were studied by measuring the incorporation of [3H]phenylalanine into mitochondrial protein using the flooding dose technique. 3. Mitochondrial protein content was reduced to 54% of that measured in the pair-fed rats and to 71% of that measured in control rats fed ad libitum 2 days after the zymosan treatment. The decreased mitochondrial protein content observed 2 days after zymosan challenge was preceded by a reduced rate of synthesis of mitochondrial protein 16h after treatment. Both changes were of greater magnitude than the general muscle wasting and the decreased rate of synthesis of mixed protein observed in the zymosan-treated rats. 4. We conclude that the acute phase of critical illness in zymosan-treated rats is characterized by a substantial reduction in muscle mitochondria that is at least in part caused by a decreased rate of synthesis of mitochondrial protein. This derangement in mitochondrial protein metabolism may be related to the impaired muscle function observed during and after critical illness.
Rooyackers
O E
OE
Department of Human Biology, University of Limburg, Maastricht, Netherlands.
Kersten
A H
AH
Wagenmakers
A J
AJ
D000818:Animals; D016638:Critical Illness; D003576:Electron Transport Complex IV / Q000378:metabolism; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D009124:Muscle Proteins / Q000096:biosynthesis / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009133:Muscular Atrophy / Q000378:metabolism; D010649:Phenylalanine / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew
D009124:Muscle Proteins; D010649:Phenylalanine; D003576:Electron Transport Complex IV