Conformational basis of energy transduction in mitochondria
The conformational mechanism of energy transduction which we proposed in 1967 was based on an intuitive evaluation of the significance of large amplitude configurational changes which parallel energized processes in mitochondria [l-3] . By now a considerable body of information has been accumulated about the details of the configurational transitions in the mitochondrion [4-61. Moreover, the theory of structured systems with the capability for conservation of energy by a conformational mechanism is now being developed systematically [7]. This interplay of experiment and theory has made it possible to formulate the conformational hypothesis more explicitly and precisely. The tripartite repeating unit of the cristal membrane is the molecular unit of mitochondrial energy transduction. While in theory each repeating unit is a complete operational unit, in practice we are dealing with two dimensional arrays of repeating units within a membrane continuum and with the cooperative effects intrinsic to such arrays. Each repeating unit contains three basic systems which collectively effectuate the conformational transduction of energy. These systems are (a) the primary energizing system (one of the complexes of the electron transfer chain), (b) the conformational frame system, and (c) the discharge-directing system (the ATPase complex is one such system). The electron transfer process within each complex of the chain leads to a conformational transition [8-lo]. But since the electron transfer system is enclosed within a rigid frame (the conformational frame system [ 7]), the conformational expansion of
Configurational changes in isolated rat liver mitochondria as revealed by negative staining. II. Modifications caused by changes in respiratory states.
The configuration of isolated rat liver mitochondria associated with the five respiratory steady states, as defined by Chance and Williams (9), have been studied in unfixed preparations negatively stained by neutral isotonic ammonium molybdate under strictly controlled conditions. Biochemical and ultrastructural analysis were carried out on the same mitochondrial population undergoing transitions from one respiratory state to another. Each respiratory state was found to be associated with either an expanded or a condensed configuration. The two configurations were characterized by the mitochondrial total volume, the thickness of the outer membrane, the morphology of the inner sac, the deepness of the inner membrane infoldings, the shape and amplitude of the intracristal spaces, and the elementary structure of the outer surface of the inner membrane. The condensed configuration corresponded to the configuration exhibited by freshly isolated resting mitochondria suspended in about 0.25 M sucrose; the expanded configuration conformed to the one shown by resting mitochondria suspended in about 0.20 M sucrose. In respiratory steady state 1 and 4 the mitochondria showed an expanded configuration; in state 2, 3, 5, and uncoupled, they exhibited a condensed configuration. Differences in the morphology of the inner sac were associated with the oxidation of pyruvate, α-oxoglutarate, or citrate. The correlations between the activity of the respiratory chain and the mitochondrial configuration have been considered, and the results have been discussed in relation with current views on the mechanisms of energy conservation in mitochondria.
A study of the local tissue reactions in man to cortisone and compound F. VI. Histopathological studies of the local effect of compound F in normal and pathologic skin of man.
After our previous negative studies (1) of the local effect of cortisone acetate in the skin of man, a year ago, a parallel study of 17-hydroxycorticosterone-21-acetate, Compound F, was outlined. Theoretically, Compound F should be the active steroid. It was so suggested by Rothman (2), that in all probability Compound F and not cortisone would be active locally in the skin of man.