Were mitochondrial contractions driving the cellular energy cycle?

Were mitochondrial contractions driving the cellular energy cycle? o, but Charles Hackenbrock's thesis work so elegantly supported the hypothesis—that a mechanochemical mechanism coupled electron transport to ATP synthe-sis—that it was cited almost 600 times as evidence. It earned him speaking invitations all over the US and Europe, and an assistant professorship at Johns Hopkins University (Baltimore, MD) straight out of graduate studies. " Everyone, " he says, " fell in love with these ultrastructural changes. " Hackenbrock, now an emeritus professor at the University of North Carolina, Chapel Hill, recalls that the project started as a graduate course project to isolate mitochondria from rat livers and test the effects of snake venom on their function. But when he noticed that his control group of mitochondria underwent a dramatic conformational change—from " knotted up " just after isolation to the " beautiful mitochondria " of intact cells—during a sucrose buffer incubation, he immediately switched his thesis to study how this structural change might correlate with oxidative phosphorylation function. " In those days, mitochondrial function in terms of making ATP was one of the key questions in biochemistry around the world, " he says. " I realized immediately this was going to be of wide interest. " At the time, the only evidence for structural changes during oxidative phosphorylation came from light-scattering studies that measured the optical density of isolated mitochondria (Chance and Packer, 1958). Lehninger (1959) first proposed that the structural changes might represent, in Hackenbrock's words, " an energy-linked mechanochemical process which may reside in a multienzyme respiratory assembly which carries out electron transport and oxidative phosphory-lation. " In one scenario for such a link, ions might be pumped across the inner membrane to generate osmotic deformation of the mitochondrion, and the resultant mechanical force might then be used by an enzyme to generate ATP. Hackenbrock developed a unique setup to correlate ultrastructural changes, light scattering, and metabolic function. Before and after addition of ADP and substrates for the electron transport chain, he measured mitochondrial optical density and oxygen consumption and fixed mitochondria for EM (Hackenbrock, 1966). The experiment revealed that mitochondria changed from a " condensed " to " orthodox " conformation while incubating in a buffer supporting slow respiration with no added ADP. Once ADP was added, however, the organelles contracted to the condensed form once again. The contractions were reversible (arguing against a fixation artifact) and seemed …