Mitochondrial ATP synthase dimers spontaneously associate due to a long-range membrane-induced force 2018

Claudio Anselmi, and Karen M Davies, and José D Faraldo-Gómez
Theoretical Molecular Biophysics Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.

Adenosine triphosphate (ATP) synthases populate the inner membranes of mitochondria, where they produce the majority of the ATP required by the cell. From yeast to vertebrates, cryoelectron tomograms of these membranes have consistently revealed a very precise organization of these enzymes. Rather than being scattered throughout the membrane, the ATP synthases form dimers, and these dimers are organized into rows that extend for hundreds of nanometers. The rows are only observed in the membrane invaginations known as cristae, specifically along their sharply curved edges. Although the presence of these macromolecular structures has been irrefutably linked to the proper development of cristae morphology, it has been unclear what drives the formation of the rows and why they are specifically localized in the cristae. In this study, we present a quantitative molecular-simulation analysis that strongly suggests that the dimers of ATP synthases organize into rows spontaneously, driven by a long-range attractive force that arises from the relief of the overall elastic strain of the membrane. The strain is caused by the V-like shape of the dimers, unique among membrane protein complexes, which induces a strong deformation in the surrounding membrane. The process of row formation is therefore not a result of direct protein-protein interactions or a specific lipid composition of the membrane. We further hypothesize that, once assembled, the ATP synthase dimer rows prime the inner mitochondrial membrane to develop folds and invaginations by causing macroscopic membrane ridges that ultimately become the edges of cristae. In this way, mitochondrial ATP synthases would contribute to the generation of a morphology that maximizes the surface area of the inner membrane, and thus ATP production. Finally, we outline key experiments that would be required to verify or refute this hypothesis.

UI MeSH Term Description Entries
D005656 Fungal Proteins Proteins found in any species of fungus. Fungal Gene Products,Fungal Gene Proteins,Fungal Peptides,Gene Products, Fungal,Yeast Proteins,Gene Proteins, Fungal,Peptides, Fungal,Proteins, Fungal
D048468 Podospora A genus of ascomycete FUNGI in the order SORDARIALES, which is found on SOIL and herbivore dung (FECES). Triangularia anserina,Podospora anserina,Podosporas
D055503 Protein Multimerization The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS. Protein Dimerization,Protein Heteromultimerizaton,Protein Multimer Assembly,Protein Trimerization,Assembly, Protein Multimer,Dimerization, Protein,Heteromultimerizaton, Protein,Heteromultimerizatons, Protein,Multimer Assembly, Protein,Multimerization, Protein,Trimerization, Protein
D056004 Molecular Dynamics Simulation A computer simulation developed to study the motion of molecules over a period of time. Molecular Dynamics Simulations,Molecular Dynamics,Dynamic, Molecular,Dynamics Simulation, Molecular,Dynamics Simulations, Molecular,Dynamics, Molecular,Molecular Dynamic,Simulation, Molecular Dynamics,Simulations, Molecular Dynamics
D025261 Mitochondrial Proton-Translocating ATPases Proton-translocating ATPases responsible for ADENOSINE TRIPHOSPHATE synthesis in the MITOCHONDRIA. They derive energy from the respiratory chain-driven reactions that develop high concentrations of protons within the intermembranous space of the mitochondria. Electron Transport Complex V,Mitochondrial ATP Synthase,Respiratory Complex V,Mitochondrial ATP Synthases,Mitochondrial F(1)F(0) ATPase,ATP Synthase, Mitochondrial,ATP Synthases, Mitochondrial,ATPases, Mitochondrial Proton-Translocating,Mitochondrial Proton Translocating ATPases,Proton-Translocating ATPases, Mitochondrial

Related Publications

Claudio Anselmi, and Karen M Davies, and José D Faraldo-Gómez
March 2019, Proceedings of the National Academy of Sciences of the United States of America,
Claudio Anselmi, and Karen M Davies, and José D Faraldo-Gómez
April 2013, Proceedings of the National Academy of Sciences of the United States of America,
Claudio Anselmi, and Karen M Davies, and José D Faraldo-Gómez
October 2007, Biophysical journal,
Claudio Anselmi, and Karen M Davies, and José D Faraldo-Gómez
January 2004, Toxicology mechanisms and methods,
Claudio Anselmi, and Karen M Davies, and José D Faraldo-Gómez
July 2011, Zhonghua er ke za zhi = Chinese journal of pediatrics,
Claudio Anselmi, and Karen M Davies, and José D Faraldo-Gómez
April 1999, Biochemical and biophysical research communications,
Claudio Anselmi, and Karen M Davies, and José D Faraldo-Gómez
July 2017, EMBO reports,
Claudio Anselmi, and Karen M Davies, and José D Faraldo-Gómez
April 2008, The EMBO journal,
Claudio Anselmi, and Karen M Davies, and José D Faraldo-Gómez
February 1988, Trends in genetics : TIG,
Claudio Anselmi, and Karen M Davies, and José D Faraldo-Gómez
October 1990, The American journal of physiology,
Copied contents to your clipboard!