Salmon spawning migration and muscle protein metabolism: the August Krogh principle at work.

The August Krogh principle, stating that for any particular question in biology, nature holds an ideal study system, was applied by choosing the anorexic, long-distance migration of salmon as a model to analyze protein degradation and amino acid metabolism. Reexamining an original study done over 20 years ago on migrating sockeye salmon (Oncorhynchus nerka), data on fish migration and starvation are reviewed and a general model is developed on how fish deal with muscle proteolysis. It is shown that lysosomal activation and degradation of muscle protein by lysosomal cathepsins, especially cathepsin D and sometimes cathepsin L, are responsible for the degradation of muscle protein during fish migration, maturation and starvation. This strategy is quite the opposite to mammalian muscle wasting, including starvation, uremia, cancer and others, where the ATP-ubiquitin proteasome in conjunction with ancillary systems, constitutes the overwhelming pathway for protein degradation in muscle. In mammals, the lysosome plays a bit part, if any. In contrast, the proteasome plays at best a subordinate role in muscle degradation in piscine systems. This diverging strategy is put into the context of fish metabolism in general, with its high amino acid turnover, reliance on amino acids as oxidative substrates and flux of amino acids from muscle via the liver into gonads during maturation. Brief focus is placed on structure, function and evolution of the key player in fishes: cathepsin D. The gene structure of piscine cathepsin D is outlined, focusing on the existence of duplicate, paralogous, cathepsin D genes in some species and analyzing the relationship between a female and liver-specific aspartyl protease and fish cathepsin Ds. Evolutionary relationships are developed between different groups of piscine cathepsins, aspartyl proteases and other cathepsins. Finally, based on specific changes in muscle enzymes in fish, including migrating salmon, common strategies of amino acid and carbon flux in fish muscle are pointed out, predicting some metabolic concepts that would make ideal application grounds for the August Krogh principle.