Structure of Mitochondrial ATP Synthase Is Solved

Technology Networks | November 19, 2019

Researchers Alexander Mühleip (Stockholm University) and Alexey Amunts (Stockholm University) solved the structure of a mitochondrial ATP synthase with native lipids. ATP synthase is a universal molecular machine for energy conversion. By coupling to cellular respiration in mitochondria, it catalyzes conversion of chemical energy of cells. Mitochondrial ATP synthase is composed of dimers that, when come together, form membrane curvature that is essential for efficient energy conversion. While the mitochondrial signature lipid cardiolipin and its interactions with proteins are believed to contribute to this process, it was not directly visualized before. In addition, it was unclear to what extent the ATP synthase has diverged across different species. Researcher Alexander Mühleip, from Amunts lab, used the single-cell photosynthetic organism Euglena gracilis, which belongs to a phylum that also includes human parasites, to extract the mitochondrial ATP synthase. Its structure was then determined using cryo-EM, allowing the reconstruction of the atomic model. The high resolution of the cryo-EM density map allowed identification of 29 different protein subunits and 25 cardiolipin molecules. Some of the cardiolipins appear to modulate the critical channel for proton transfer that fuels the machine, which is the first evidence for their direct involvement.

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