bims-resufa 2023-11-12 papers

Proc Natl Acad Sci U S A. 2023 Nov 14. 120(46): e2307697120

Structure and function of the S. pombe III-IV-cyt c supercomplex.

Agnes Moe, Anna-Roza Dimogkioka, Doron Rapaport, Linda Näsvik Öjemyr, Peter Brzezinski.

The respiratory chain in aerobic organisms is composed of a number of membrane-bound protein complexes that link electron transfer to proton translocation across the membrane. In mitochondria, the final electron acceptor, complex IV (CIV), receives electrons from dimeric complex III (CIII2), via a mobile electron carrier, cytochrome c. In the present study, we isolated the CIII2CIV supercomplex from the fission yeast Schizosaccharomyces pombe and determined its structure with bound cyt. c using single-particle electron cryomicroscopy. A respiratory supercomplex factor 2 was found to be bound at CIV distally positioned in the supercomplex. In addition to the redox-active metal sites, we found a metal ion, presumably Zn2+, coordinated in the CIII subunit Cor1, which is encoded by the same gene (qcr1) as the mitochondrial-processing peptidase subunit β. Our data show that the isolated CIII2CIV supercomplex displays proteolytic activity suggesting a dual role of CIII2 in S. pombe. As in the supercomplex from S. cerevisiae, subunit Cox5 of CIV faces towards one CIII monomer, but in S. pombe, the two complexes are rotated relative to each other by ~45°. This orientation yields equal distances between the cyt. c binding sites at CIV and at each of the two CIII monomers. The structure shows cyt. c bound at four positions, but only along one of the two symmetrical branches. Overall, this combined structural and functional study reveals the integration of peptidase activity with the CIII2 respiratory system and indicates a two-dimensional cyt. c diffusion mechanism within the CIII2-CIV supercomplex.

Keywords: bioenergetics; cytochrome bc1; cytochrome c oxidase; electron transfer; mitochondria

DOI: https://doi.org/10.1073/pnas.2307697120

Enzymes. 2023 ;pii: S1874-6047(23)00004-5. [Epub ahead of print]54 15-36

The mitochondrial respiratory chain.

Mårten Wikström, Cristina Pecorilla, Vivek Sharma.

We present a brief review of the mitochondrial respiratory chain with emphasis on complexes I, III and IV, which contribute to the generation of protonmotive force across the inner mitochondrial membrane, and drive the synthesis of ATP by the process called oxidative phosphorylation. The basic structural and functional details of these complexes are discussed. In addition, we briefly review the information on the so-called supercomplexes, aggregates of complexes I-IV, and summarize basic physiological aspects of cell respiration.

Keywords: Bioenergetics; Cell respiration; Cytochromes; Electron transfer; Oxidative phosphorylation; Oxygen consumption; Proton pumping; Proton transfer; Protonmotive force; Supercomplexes

DOI: https://doi.org/10.1016/bs.enz.2023.05.001

EMBO J. 2023 Nov 07. e114054

Cristae formation is a mechanical buckling event controlled by the inner mitochondrial membrane lipidome.

Kailash Venkatraman, Christopher T Lee, Guadalupe C Garcia, Arijit Mahapatra, Daniel Milshteyn, Guy Perkins, Keun-Young Kim, H Amalia Pasolli, Sebastien Phan, Jennifer Lippincott-Schwartz, Mark H Ellisman, Padmini Rangamani, Itay Budin.

Cristae are high-curvature structures in the inner mitochondrial membrane (IMM) that are crucial for ATP production. While cristae-shaping proteins have been defined, analogous lipid-based mechanisms have yet to be elucidated. Here, we combine experimental lipidome dissection with multi-scale modeling to investigate how lipid interactions dictate IMM morphology and ATP generation. When modulating phospholipid (PL) saturation in engineered yeast strains, we observed a surprisingly abrupt breakpoint in IMM topology driven by a continuous loss of ATP synthase organization at cristae ridges. We found that cardiolipin (CL) specifically buffers the inner mitochondrial membrane against curvature loss, an effect that is independent of ATP synthase dimerization. To explain this interaction, we developed a continuum model for cristae tubule formation that integrates both lipid and protein-mediated curvatures. This model highlighted a snapthrough instability, which drives IMM collapse upon small changes in membrane properties. We also showed that cardiolipin is essential in low-oxygen conditions that promote PL saturation. These results demonstrate that the mechanical function of cardiolipin is dependent on the surrounding lipid and protein components of the IMM.

Keywords: cardiolipin; cristae; lipids; mechanics; mitochondria

DOI: https://doi.org/10.15252/embj.2023114054