scholarly journals Molecular characterization of a complex of Apoptosis Inducing Factor 1 (AIFM1) with cytochrome c oxidase of the mitochondrial respiratory chain

2021 ◽  
Author(s):  
Johannes F Hevler ◽  
Riccardo Zenezini Chiozzi ◽  
Alfredo Cabrera-Orefice ◽  
Ulrich Brandt ◽  
Susanne Arnold ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Respiratory Chain ◽  
Structural Model ◽  
Direct Electron Transfer ◽  
Mitochondrial Respiratory Chain ◽  
Structural Restraints ◽  
Apoptosis Inducing Factor

Combining mass spectrometry based chemical cross-linking and complexome profiling, we analyzed the interactome of heart mitochondria. We focused on complexes of oxidative phosphorylation and found that dimeric apoptosis inducing factor 1 (AIFM1) forms a defined complex with ~10% of monomeric cytochrome c oxidase (COX), but hardly interacts with respiratory chain supercomplexes. Multiple AIFM1 inter-crosslinks engaging six different COX subunits provided structural restraints to build a detailed atomic model of the COX-AIFM12 complex. Application of two complementary proteomic approaches thus provided unexpected insight into the macromolecular organization of the mitochondrial complexome. Our structural model excludes direct electron transfer between AIFM1 and COX. Notably however, the binding site of cytochrome c remains accessible allowing formation of a ternary complex. The discovery of the previously overlooked COX-AIFM12 complex and clues provided by the structural model hint at a role of AIFM1 in OXPHOS biogenesis and in programmed cell death.

scholarly journals Molecular characterization of a complex of apoptosis-inducing factor 1 with cytochrome c oxidase of the mitochondrial respiratory chain

2021 ◽  
Vol 118 (39) ◽  
pp. e2106950118
Author(s):  
Johannes F. Hevler ◽  
Riccardo Zenezeni Chiozzi ◽  
Alfredo Cabrera-Orefice ◽  
Ulrich Brandt ◽  
Susanne Arnold ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Respiratory Chain ◽  
Structural Model ◽  
Direct Electron Transfer ◽  
Mitochondrial Respiratory Chain ◽  
Structural Restraints ◽  
Apoptosis Inducing Factor ◽  
Insight Into ◽  
Macromolecular Organization

Combining mass spectrometry–based chemical cross-linking and complexome profiling, we analyzed the interactome of heart mitochondria. We focused on complexes of oxidative phosphorylation and found that dimeric apoptosis-inducing factor 1 (AIFM1) forms a defined complex with ∼10% of monomeric cytochrome c oxidase (COX) but hardly interacts with respiratory chain supercomplexes. Multiple AIFM1 intercross-links engaging six different COX subunits provided structural restraints to build a detailed atomic model of the COX-AIFM12 complex (PDBDEV_00000092). An application of two complementary proteomic approaches thus provided unexpected insight into the macromolecular organization of the mitochondrial complexome. Our structural model excludes direct electron transfer between AIFM1 and COX. Notably, however, the binding site of cytochrome c remains accessible, allowing formation of a ternary complex. The discovery of the previously overlooked COX-AIFM12 complex and clues provided by the structural model hint at potential roles of AIFM1 in oxidative phosphorylation biogenesis and in programmed cell death.

Carbon Monoxide Specifically Inhibits Cytochrome C Oxidase of Human Mitochondrial Respiratory Chain

2003 ◽  
Vol 93 (3) ◽  
pp. 142-146 ◽  
Author(s):  
Jose-Ramon Alonso ◽  
Francesc Cardellach ◽  
Sònia López ◽  
Jordi Casademont ◽  
Òscar Miró
Keyword(s):  
Carbon Monoxide ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Respiratory Chain ◽  
Mitochondrial Respiratory Chain ◽  
Mitochondrial Respiratory

New perspectives on the assembly process of mitochondrial respiratory chain complex cytochrome c oxidase

Mitochondrion ◽  
2002 ◽  
Vol 2 (1-2) ◽  
pp. 117-128 ◽  
Author(s):  
Cristina Ugalde ◽  
Marieke J.H Coenen ◽  
Murtada H Farhoud ◽  
Stefanie Gilinsky ◽  
Werner J.H Koopman ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Respiratory Chain ◽  
Chain Complex ◽  
Mitochondrial Respiratory Chain ◽  
Assembly Process ◽  
Respiratory Chain Complex ◽  
Mitochondrial Respiratory Chain Complex ◽  
Mitochondrial Respiratory

scholarly journals The Role of COA6 in the Mitochondrial Copper Delivery Pathway to Cytochrome c Oxidase

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 125
Author(s):  
Abhinav B. Swaminathan ◽  
Vishal M. Gohil
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Mitochondrial Respiratory Chain ◽  
Functional Studies ◽  
Evolutionarily Conserved ◽  
Human Disorders ◽  
The Stability ◽  
Copper Delivery

Copper is essential for the stability and activity of cytochrome c oxidase (CcO), the terminal enzyme of the mitochondrial respiratory chain. Copper is bound to COX1 and COX2, two core subunits of CcO, forming the CuB and CuA sites, respectively. Biogenesis of these two copper sites of CcO occurs separately and requires a number of evolutionarily conserved proteins that form the mitochondrial copper delivery pathway. Pathogenic mutations in some of the proteins of the copper delivery pathway, such as SCO1, SCO2, and COA6, have been shown to cause fatal infantile human disorders, highlighting the biomedical significance of understanding copper delivery mechanisms to CcO. While two decades of studies have provided a clearer picture regarding the biochemical roles of SCO1 and SCO2 proteins, some discrepancy exists regarding the function of COA6, the new member of this pathway. Initial genetic and biochemical studies have linked COA6 with copper delivery to COX2 and follow-up structural and functional studies have shown that it is specifically required for the biogenesis of the CuA site by acting as a disulfide reductase of SCO and COX2 proteins. Its role as a copper metallochaperone has also been proposed. Here, we critically review the recent literature regarding the molecular function of COA6 in CuA biogenesis.

scholarly journals The [PSI+] prion and HSP104 modulate cytochrome c oxidase deficiency caused by deletion of COX12

2021 ◽  
Author(s):  
Pawan Kumar Saini ◽  
Hannah Dawitz ◽  
Andreas Aufschnaiter ◽  
Jinsu Thomas ◽  
Amelie Amblard ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Respiratory Chain ◽  
Experimental Evolution ◽  
Mitochondrial Respiratory Chain ◽  
Oxidase Deficiency ◽  
Functional Connection ◽  
Amyloid Aggregates ◽  
Exact Function ◽  
Mitochondrial Respiratory

Cytochrome c oxidase is a pivotal enzyme of the mitochondrial respiratory chain, which sustains bioenergetics of eukaryotic cells. Cox12, a peripheral subunit of cytochrome c oxidase, is required for full activity of the enzyme, but its exact function is unknown. Here, experimental evolution of a Saccharomyces cerevisiae Δcox12 strain for ≈300 generations allowed to restore the activity of cytochrome c oxidase. In one population, the enhanced bioenergetics was caused by a A375V mutation in the AAA+ disaggregase Hsp104. Deletion or overexpression of Hsp104 also increased respiration of the Δcox12 ancestor strain. This beneficial effect of Hsp104 was related to the loss of the [PSI+] prion, which forms cytosolic amyloid aggregates of the Sup35 protein. Overall, our data demonstrate that cytosolic aggregation of a prion impairs the mitochondrial metabolism of cells defective for Cox12. These findings identify a new functional connection between cytosolic proteostasis and biogenesis of the mitochondrial respiratory chain.

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