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
Biochemical lesions of respiratory enzymes and configurational changes of mitochondria in vivo
SummaryChick embryo heart fragments in primary hanging-drop culture were treated with sodium fluoroacetate to induce inhibition of aconitate hydratase, a mitochondrial enzyme of the tricarboxylic acid cycle. The mitochondria were analyzed in the living myoblasts by phase-contrast time-lapse cinemicrography. The results were recorded in a 16 mm film. After 20–30 minutes contact of the cells with the inhibitor some mitochondria became thickened and swollen. The swelling was polymorphous, asynchronous and reversible; the same mitochondrion could swell and shrink many times. Some mitochondria seemed not to respond to fluoroacetate and remained rod-like. Mitochondria appeared the only cell components to be morphologically affected by fluoroacetate and the changes were specifically caused by the inhibitor. The type of mitochondrial swelling differed from the large-amplitude respiration-dependent swelling of the isolated mitochondria in vitro and from the configurational changes of isolated mitochondria associated with the respiratory states. The evidence pointed to a specific connection between the biochemical lesion caused by fluoroacetate and the configurational changes of the mitochondria. The mitochondrial swelling was to a large extent reversed by washing the cultures with Tyrode physiological saline solution and the reversal was further accentuated by incubation of the cultures in fresh nutrient medium.
Passive induction of the "energized-twisted" conformational state in bovine heart mitochondria.
Abstract It is demonstrated that hypotonically-swollen bovine heart mitochondria undergo transformation into the “energized-twisted” conformational state ( Green et al. Arch. Biochem. Biophys. 125:684, 1968 ) when simultaneously exposed to glutaraldehyde fixative and induced to contract by passive osmotic means. It is suggested that this passively-induced transformation and energy-dependent transformation of mitochondria into the “energized-twisted” state occur by similar mechanisms.