Components of the Energy-Coupling Mechanism and 

 Mitochondrial Structure* 



Albert L. Lehxixger 



Department of Physiological Chemistry, The Johns Hopkins ScJiool of 

 Medicine, Baltimore, Md., U.S.A. 



In this paper approaches taken in our laboratory to the isolation and 

 identification of active mitochondrial proteins involved in the mechanism 

 of respiratory energy-coupling and in the mitochondrial swelling and 

 contraction cycle will be described. This information is still only frag- 

 mentary, but it gives increasing hope that the mechanism of oxidative 

 phosphorylation, the structure of the mitochondrial membranes, and the 

 physical nature of swelling and contraction may be studied in molecular 

 terms and that these entities may ultimately be at least partlv reconstructed 

 in vitro from the isolated catalysts. 



Although considerable progress has been made bv biochemists in the 

 study of the mitochondrion actually much of this work has involved 

 study of the more organized physiology of the mitochondrion, its control 

 mechanisms, and the action of hormones and drugs. The major reason, 

 without question, for our lack of specific molecular knowledge of mito- 

 chondrial chemistry is the fact that the most interesting of the mito- 

 chondrial reactions take place in what I once designated as a "solid-state 

 enzyme system" [i], namely the insoluble complex lipoprotein structure 

 of the mitochondrial membranes, which contain the assemblies of res- 

 piratory enzymes. Since the first efforts of Warburg and Keilin many 

 years ago, the respiratory enzymes in these membranes have been found 

 to be remarkably refractory to isolation in soluble, homogeneous form. 

 The relatively limited information we now have available on the respiratorv 

 carriers and coupling enzymes, as isolated molecular entities, has figura- 

 tively had to be carved out of solid rock. The direct approach to chemical 

 study of the molecular components of the mitochondrion has thus been 

 forbidding and frustrating, and has given rise to development of indirect 

 methods and sometimes less than direct study objectives. 



* Original work in the author's laboratory was supported by grants from the 

 National Institutes of Health, the National Science Foundation, the Nutrition 

 Foundation, Inc., and the Whitehall Foundation. 



