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Electron transfer in the respiratory chain at low salinity.
Ana Paula Lobez1, Fei Wu1, Justin M Di Trani2,3
1Department of Biochemistry and Biophysics, The Arrhenius Laboratories for Natural Sciences, Stockholm University, Stockholm, Sweden.
Nature Communications
|September 19, 2024
Summary
Electrostatic interactions are key for cellular respiration. Multiple cytochrome c molecules bind to the supercomplex III2-IV, facilitated by structured CIII2 loops, enabling efficient electron transfer.
Area of Science:
- Mitochondrial respiration
- Protein-protein interactions
- Biophysics
Background:
- Cellular electrostatic interactions play a crucial role in biological processes.
- Cytochrome c (cyt. c) is a key electron carrier in the mitochondrial respiratory chain.
- The supercomplex III2-IV is a major component of the electron transport chain.
Purpose of the Study:
- To investigate the electrostatic interactions between cyt. c and the supercomplex III2-IV from Saccharomyces cerevisiae.
- To elucidate the structural basis of electron transfer at low salinity.
Main Methods:
- Cryo-electron microscopy (cryo-EM) at 2.4 Å resolution.
- Steady-state kinetic studies.
- Analysis of protein structure and molecular interactions.
Main Results:
- Multiple cyt. c molecules bind to the supercomplex III2-IV surface, indicated by kinetic studies (Hill coefficient ≥2) and cryo-EM data.
- Negatively charged loops of CIII2 subunits (Qcr6, Qcr9) become structured to interact with cyt. c.
- Water molecules in CIV proton pathways and cardiolipin molecules were identified at higher resolution.
Conclusions:
- Lowered electrostatic screening facilitates the engagement of multiple cyt. c molecules.
- Electrostatically structured CIII2 loops direct cyt. c binding for efficient electron transfer between CIII2 and CIV.
- This study provides novel insights into the mechanism of mitochondrial electron transport.
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