Proton-transfer pathways in the mitochondrial S. cerevisiae cytochrome c oxidase

Björck, Markus L.; Vilhjálmsdóttir, Jóhanna; Hartley, Andrew M.; Meunier, Brigitte; Öjemyr, Linda Näsvik; Maréchal, Amandine; Brzezinski, Peter

doi:10.1038/s41598-019-56648-9

Cited by 13 publications

(10 citation statements)

References 38 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The structure and function of the K and D proton pathways have been studied in detail in bacterial A1-type Cy-tcOs, 129,130,137−150 and their involvement in proton uptake also confirmed for the S. cerevisiae mitochondrial CytcO. 151,152 The K pathway starts near Glu82 in subunit II at the membrane n side (Figure 5B). It is connected via a water molecule to Ser256, which is hydrogen-bonded to the conserved Lys319.…”

Section: The Catalytic Reaction and Proton Pathwaysmentioning

confidence: 81%

“…165 Structural analyses and data from functional studies of structural variants in which putative residues of the H pathway were modified in the mitochondrial S. cerevisiae CytcO do not support a functional role of this pathway. 151,152,166 Furthermore, key residues of the suggested H pathway are not present in CytcO from plant mitochondria, 32 which suggest that its involvement in proton pumping would have to be restricted to the mammalian CytcOs.…”

Section: The Catalytic Reaction and Proton Pathwaysmentioning

confidence: 99%

See 1 more Smart Citation

Structure and Mechanism of Respiratory III–IV Supercomplexes in Bioenergetic Membranes

2021

Self Cite

View full text Add to dashboard Cite

In the final steps of energy conservation in aerobic organisms, free energy from electron transfer through the respiratory chain is transduced into a proton electrochemical gradient across a membrane. In mitochondria and many bacteria, reduction of the dioxygen electron acceptor is catalyzed by cytochrome c oxidase (complex IV), which receives electrons from cytochrome bc 1 (complex III), via membrane-bound or watersoluble cytochrome c. These complexes function independently, but in many organisms they associate to form supercomplexes. Here, we review the structural features and the functional significance of the nonobligate III 2 IV 1/2 Saccharomyces cerevisiae mitochondrial supercomplex as well as the obligate III 2 IV 2 supercomplex from actinobacteria. The analysis is centered around the Q-cycle of complex III, proton uptake by CytcO, as well as mechanistic and structural solutions to the electronic link between complexes III and IV. CONTENTS 1. Introduction 9645 2. Complex III 9648 2.1. Catalytic Reaction and Quinone Binding 9649 2.2. The Bifurcated Electron Transfer 9650 2.2.1. Canonical Complex III 9650 2.2.2. M. smegmatis and C. glutamicum Supercomplexes 9651 2.3. Proton Release from the Q P Site 9651 2.3.1. Canonical Complex III 9651 2.3.2. M. smegmatis and C. glutamicum Supercomplexes 9651 3. Complex IV 9652 3.1. The Core Subunits 9653 3.2. The Catalytic Reaction and Proton Pathways 9653 3.3. Peripheral subunits of the S. cerevisiae CytcO 9654 3.4. The M. smegmatis CytcO 9654 3.5. Nonredox Active Metal Sites 9655 3.6. The Putative CytcO Dimer 9655 4. Complex III−IV Supercomplexes 9656 4.1. The S. cerevisiae Supercomplex 9656 4.2. Other (I)III 2 IV 1/2 Supercomplexes 9656 4.3. Cardiolipin in Supercomplexes 9657 4.4. Respiratory Supercomplex Factors 9658 4.5. Superoxide Dismutase in the M. smegmatis Supercomplex 9658 5. Interaction of Complexes III 2 and IV with Cytochrome c 9659 5.1. Cyt. c Binding to Complexes III and IV 9659 5.2. The Electronic Link between Complexes III and IV 5.2.1. Diffusion in 3D 5.2.2. Diffusion in 2D 5.2.3. Effects of Cox5/cyt. c Isoforms 5.2.4. Binding of cyt. c to Rcf1 6. Why Supercomplexes? 6.1. Changes in Structure or Activity upon Formation of Supercomplexes 6.2. Protein Distribution and Aggregation 6.3. Production of ROS 6.4. Free Energy Conservation 6.5. The Redox State and Binding of cyt. c

show abstract

Section: The Catalytic Reaction and Proton Pathwaysmentioning

confidence: 81%

Section: The Catalytic Reaction and Proton Pathwaysmentioning

confidence: 99%

Structure and Mechanism of Respiratory III–IV Supercomplexes in Bioenergetic Membranes

2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…The inhibitory effects of T316K and E243D are consistent with observations in variants of the equivalent T359 of R. sphaeroides (38,39), as well as with E/D replacement of the residue equivalent to E243 in E. coli (40), P. denitrificans (31), and R. sphaeroides (41). We previously showed that yeast mutant I67N (42), for which no equivalent bacterial mutant has been studied, is likely to interfere directly with E243 function at the top of the D-channel (43,44) and to compromise substrate proton uptake (45,46). These effects clearly confirm the expected essential roles of the D-and K-pathways in catalysis.…”

Section: Discussionmentioning

confidence: 99%

A common coupling mechanism for A-type heme-copper oxidases from bacteria to mitochondria

Maréchal

Genko

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Mitochondria metabolize almost all the oxygen that we consume, reducing it to water by cytochrome c oxidase (CcO). CcO maximizes energy capture into the protonmotive force by pumping protons across the mitochondrial inner membrane. Forty years after the H+/e− stoichiometry was established, a consensus has yet to be reached on the route taken by pumped protons to traverse CcO’s hydrophobic core and on whether bacterial and mitochondrial CcOs operate via the same coupling mechanism. To resolve this, we exploited the unique amenability to mitochondrial DNA mutagenesis of the yeast Saccharomyces cerevisiae to introduce single point mutations in the hydrophilic pathways of CcO to test function. From adenosine diphosphate to oxygen ratio measurements on preparations of intact mitochondria, we definitely established that the D-channel, and not the H-channel, is the proton pump of the yeast mitochondrial enzyme, supporting an identical coupling mechanism in all forms of the enzyme.

show abstract

“…Complex proton transfer pathways . The P-side of all CcOs has a tangled cluster of strongly interacting polar and protonatable residues that do not provide an obvious single exit path, although linear paths have been suggested ( Popović and Stuchebrukhov, 2005 ; Björck et al, 2019 ). The hydrogen bond network on the P-side of A- and B-type CcO, was analyzed using Monte Carlo sampling and network analysis ( Cai et al, 2018 ; Cai et al, 2020 ).…”

Section: Cytochrome C Oxidasementioning

confidence: 99%

Protein Motifs for Proton Transfers That Build the Transmembrane Proton Gradient

et al. 2021

View full text Add to dashboard Cite

Biological membranes are barriers to polar molecules, so membrane embedded proteins control the transfers between cellular compartments. Protein controlled transport moves substrates and activates cellular signaling cascades. In addition, the electrochemical gradient across mitochondrial, bacterial and chloroplast membranes, is a key source of stored cellular energy. This is generated by electron, proton and ion transfers through proteins. The gradient is used to fuel ATP synthesis and to drive active transport. Here the mechanisms by which protons move into the buried active sites of Photosystem II (PSII), bacterial RCs (bRCs) and through the proton pumps, Bacteriorhodopsin (bR), Complex I and Cytochrome c oxidase (CcO), are reviewed. These proteins all use water filled proton transfer paths. The proton pumps, that move protons uphill from low to high concentration compartments, also utilize Proton Loading Sites (PLS), that transiently load and unload protons and gates, which block backflow of protons. PLS and gates should be synchronized so PLS proton affinity is high when the gate opens to the side with few protons and low when the path is open to the high concentration side. Proton transfer paths in the proteins we describe have different design features. Linear paths are seen with a unique entry and exit and a relatively straight path between them. Alternatively, paths can be complex with a tangle of possible routes. Likewise, PLS can be a single residue that changes protonation state or a cluster of residues with multiple charge and tautomer states.

show abstract

Proton-transfer pathways in the mitochondrial S. cerevisiae cytochrome c oxidase

Cited by 13 publications

References 38 publications

Structure and Mechanism of Respiratory III–IV Supercomplexes in Bioenergetic Membranes

Structure and Mechanism of Respiratory III–IV Supercomplexes in Bioenergetic Membranes

A common coupling mechanism for A-type heme-copper oxidases from bacteria to mitochondria

Protein Motifs for Proton Transfers That Build the Transmembrane Proton Gradient

Contact Info

Product

Resources

About