Christoph Gerle

The molecular identity of the mitochondrial megachannel (MMC)/permeability transition pore (PTP), a key effector of cell death, remains controversial. By combining highly purified, fully active bovine F-ATP synthase with preformed liposomes we show that Ca²⁺ dissipates the H⁺ gradient generated by ATP hydrolysis. After incorporation of the same preparation into planar lipid bilayers Ca²⁺ elicits currents matching those of the MMC/PTP. Currents were fully reversib

The mitochondrial permeability transition is an inner mitochondrial membrane event involving the opening of the permeability transition pore concomitant with a sudden efflux of matrix solutes and breakdown of membrane potential. The mitochondrial F(o)F(1) ATP synthase has been proposed as the molecular identity of the permeability transition pore. The likeliness of potential pore-forming sites in the mitochondrial F(o)F(1) ATP synthase is discussed and a new model, the death finger model, is des

The current state of research on the mitochondrial permeability transition pore (PTP) can be described in terms of three major problems: molecular identity, atomic structure and gating mechanism. In this review these three problems are discussed in the light of recent findings with special emphasis on the discovery that the PTP is mitochondrial F-ATP synthase (mtF_oF₁). Novel features of the mitochondrial F-ATP synthase emerging from the success of single particle cryo elect

Photosystem I (PSI) is a light driven electron pump transferring electrons from Cytochrome c₆ (Cyt c₆) to Ferredoxin (Fd). An understanding of this electron transfer process is hampered by a paucity of structural detail concerning PSI:Fd interface and the possible binding sites of Cyt c₆. Here we describe the high resolution cryo-EM structure of Thermosynechococcus elongatus BP-1 PSI in complex with Fd and a loosely bound Cyt c₆. Side chain interaction

Functional reintegration into lipid environments represents a major challenge for <i>in vitro</i> investigation of integral membrane proteins (IMPs). Here, we report a new approach, termed LMNG Auto-insertion Reintegration (LAiR), for reintegration of IMPs into lipid bilayers within minutes. The resulting proteoliposomes displayed an unprecedented capability to maintain proton gradients and long-term stability. LAiR allowed for monitoring catalysis of a membrane-bound, physiologically relevant p

Of all the macromolecular assemblies of life, the least understood is the biomembrane. This is especially true in regard to its atomic structure. Ideas on biomembranes, developed in the last 200 years, culminated in the fluid mosaic model of the membrane. In this essay, I provide a historical outline of how we arrived at our current understanding of biomembranes and the models we use to describe them. A selection of direct experimental findings on the nano-scale structure of biomembranes is take

Mitochondrial cytochrome c oxidase utilizes electrons provided by cytochrome c for the active vectorial transport of protons across the inner mitochondrial membrane through the reduction of molecular oxygen to water. Direct structural evidence on the transient cytochrome c oxidase-cytochrome c complex thus far, however, remains elusive and its physiological relevant oligomeric form is unclear. Here, we report on the 2D crystallization of monomeric bovine cytochrome c oxidase with tightly bound c

Photosystem I (PSI) from the green alga Chlamydomonas reinhardtii, with various numbers of membrane bound antenna complexes (LHCI), has been described in great detail. In contrast, structural characterization of soluble binding partners is less advanced. Here, we used X-ray crystallography and single particle cryo-EM to investigate three structures of the PSI-LHCI supercomplex from Chlamydomonas reinhardtii. An X-ray structure demonstrates the absence of six chlorophylls from the luminal side of

Practical and conceptual barriers have kept human F-ATP synthase out of reach as a target for the treatment of human diseases. Although this situation has persisted for decades, it may change in the near future. In this review the principal functionalities of human F-ATP synthase--proton motive force / ATP interconversion, membrane bending and mitochondrial permeability transition--are surveyed in the context of their respective potential for pharmaceutical intervention. Further, the technical r

Mammalian F-ATP synthase is central to mitochondrial bioenergetics and is present in the inner mitochondrial membrane in a dynamic oligomeric state of higher oligomers, tetramers, dimers, and monomers. In vitro investigations of mammalian F-ATP synthase are often limited by the ability to purify the oligomeric forms present in vivo at a quantity, stability, and purity that meets the demand of the planned experiment. We developed a purification approach for the isolation of bovine F-ATP synthase

Abstract Single particle cryo electron microscopy (cryo‐EM) is now the major method for the determination of integral membrane protein structure. For the success of a given project the type of membrane mimetic used for extraction from the native cell membrane, purification to homogeneity and finally cryo‐grid vitrification is crucial. Although small molecule amphiphiles – detergents – are the most widely used membrane mimetic, specific tailoring of detergent structure for single particle cryo‐EM

The membrane domain of rotary ATPases (Fo/Vo/Ao) contains a membrane-embedded rotor ring which rotates against an adjacent cation channel-forming subunit during catalysis. The mechanism that allows stabilization of the highly mobile and yet tightly connected domains during operation while not impeding rotation is unknown. Remarkably, all known ATPase rotor rings are filled by lipids. In the crystal structure of the rotor ring of a V-ATPase from <i>Enterococcus hirae</i> the ring filling lipids f