Most of the energy found in food is converted in our cells into ATP, a versatile energy carrier that enables many biochemical reactions. This energy conversion takes place in cellular structures termed mitochondria, from where the newly synthesised ATP is exported and distributed in the entire cell for use. In the early 1950, pioneering electron microscopy work by Fritjof Sjöstrand from the Karolinska Institute revealed the first ultrastructure of mitochondria with the characteristic inner membrane invaginations termed cristae. Using modern electron microscopy techniques and other analyses, it was demonstrated during the last decade that the cristae membranes host the respiratory chain complexes and ATP synthase, the enzymes responsible for the energy conversion from food to ATP. In this process called chemiosmosis, electrons extracted from food molecules are imported into mitochondria, where they eventually react with molecular oxygen in a highly exergonic process. The released energy is stored in an electrochemical proton gradient across the cristae membrane that can be used by the ATP synthase for ATP production. The significance of the cristae membrane organization for these energy conversion processes, however, has been unclear. In a recent report, an international team including researchers from the Department of Biochemistry and Biophysics propose a solution to this long-standing question.
In the current study, a genetically engineered pH sensor was placed at specific locations within the mitochondrial membranes, allowing to estimate local pH values within this organelle in living cells. Correct localization of the pH sensors was verified by fluorescence and electron microscopy analysis. Surprisingly, the measured pH gradient was very small and not sufficient to allow for ATP production in a minimal system using purified ATP synthase embedded in membrane vesicles. Moreover, the measured pH values were hardly permitting ATP synthesis even under thermodynamically sufficient conditions.
“At first, the data were quite confusing despite we were confident that our measurements were correct”, says Martin Ott, a corresponding author of this study. “But then our collaboration partners at the University of Bern made the observation that it only needs an active proton pump from the respiratory chain in the minimal system for it to work. Now things made a lot of sense. The activity of the respiratory chain and the ATP synthase need to be very close together to function. This in turn explains why mitochondria have cristae membranes, where both activities are highly enriched and in close proximity. These findings are in accordance with earlier measurements in bacterial membranes, which are the direct ancestors of the mitochondrial inner membrane. Overall, this was a very stimulating collaboration, where each of the three labs contributed essential expertise. Without each other, this study would not have worked out.”
Link to the study: https://www.pnas.org/content/early/2020/01/17/1917968117
Link to the lab of Martin Ott, Stockholm University: https://www.su.se/english/profiles/mott-1.189661
Link to the lab of Christoph von Ballmoos, University of Bern, Switzerland: http://vonballmoos.dcb.unibe.ch/
Link to the lab of Stefan Jakobs, Max Plank Institute for Biophysical Chemistry, Germany:
