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.

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 Inhibition of Mitochondrial Complex Function—The Hepatotoxicity Mechanism of Emodin Based on Quantitative Proteomic Analyses

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 263 ◽  
Author(s):  
Longfei Lin ◽  
Yuling Liu ◽  
Sai Fu ◽  
Changhai Qu ◽  
Hui Li ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Oxidative Phosphorylation ◽  
Respiratory Chain ◽  
Mitochondrial Respiratory Chain ◽  
Mitochondrial Damage ◽  
Differentially Expressed ◽  
Traditional Chinese Medicines ◽  
Differentially Expressed Proteins ◽  
Hepatocyte Apoptosis ◽  
Chinese Medicines

Emodin is the main component of traditional Chinese medicines including rhubarb, Polygonum multiflorum, and Polygonum cuspidatum. It has confirmed hepatotoxicity and may be the main causative agent of liver damage associated with the above-mentioned traditional Chinese medicines. However, current research does not explain the mechanism of emodin in hepatotoxicity. In this study, L02 cells were used as a model to study the mechanism of emodin-induced hepatocyte apoptosis using quantitative proteomics, and the results were verified by Western blot. A total of 662 differentially expressed proteins were discovered and analyzed using Gene Ontology (GO) and pathway enrichment analysis. The results show that the oxidative phosphorylation pathway is highly represented. Abnormalities in this pathway result in impaired mitochondrial function and represent mitochondrial damage. This result is consistent with mitochondria membrane potential measurements. Analysis of differentially expressed proteins revealed that emodin mainly affects oxidative phosphorylation pathways by inhibiting the function of the mitochondrial respiratory chain complexes; the mitochondrial respiratory chain complex activity assay result also confirmed that emodin could inhibit the activity of all mitochondrial complexes. This results in an increase in caspase-3, a decrease in mitochondrial membrane potential (MMP,) an increase in reactive oxygen species (ROS), and disorders in ATP synthesis, etc., eventually leading to mitochondrial damage and hepatocyte apoptosis in vitro.

P5.37 Characterization of muscle biopsies in Mitochondrial respiratory chain disorders

2011 ◽  
Vol 21 (9-10) ◽  
pp. 735
Author(s):  
A.L. Massano ◽  
R. Teotónio ◽  
O. Rebelo ◽  
M. Grazina ◽  
P. Garcia ◽  
...  
Keyword(s):  
Respiratory Chain ◽  
Mitochondrial Respiratory Chain ◽  
Muscle Biopsies ◽  
Respiratory Chain Disorders ◽  
Mitochondrial Respiratory

scholarly journals Isolation and Properties of Human Platelet Mitochondria

Blood ◽  
1973 ◽  
Vol 42 (6) ◽  
pp. 913-918 ◽  
Author(s):  
Miriam H. Fukami ◽  
Leon Salganicoff
Keyword(s):  
Oxidative Phosphorylation ◽  
Respiratory Chain ◽  
Mitochondrial Respiration ◽  
Human Platelet ◽  
Mitochondrial Respiratory Chain ◽  
Pyridine Nucleotide ◽  
Mitochondrial Fraction ◽  
Human Platelets ◽  
Difference Spectra ◽  
Outer Membranes

Abstract A mitochondrial fraction of human platelets that exhibited respiration coupled to ADP utilization has been isolated. These activities were sensitive to classical inhibitors of mitochondrial respiration and oxidative phosphorylation. Pyridine nucleotide-linked substrates were oxidized at low rates (4-7 natoms/min/ mg), but succinate and α-glycerophosphate were oxidized more rapidly (16 and 38 natoms/min/mg, respectively). Difference spectra showed the presence of the mitochondrial respiratory chain cytochromes, c1 + c, b, and a + a3. Electron micrographs revealed the presence of intact mitochondria with well-preserved outer membranes, as well as various α-granules. There appeared to be no qualitative differences between these human platelet mitochondria and pig platelet mitochondria isolated by the same procedure.

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