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A Dynamic Substrate Pool Revealed by cryo-EM of a Lipid-Preserved Respiratory Supercomplex
Tae Jin Jeon1,2, Seong-Gyu Lee3,4, Suk Hyun Yoo1
1Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Korea.
Antioxidants & Redox Signaling
|December 16, 2021
Summary
Mitochondrial respiratory supercomplexes exhibit dynamic movements, facilitated by phospholipids, creating a substrate pool for efficient electron transfer and metabolic regulation.
Area of Science:
- Biochemistry
- Structural Biology
- Mitochondrial Biology
Background:
- Mitochondrial respiratory supercomplexes are crucial for ATP synthesis via redox electron transfer.
- Understanding supercomplex structure and function under physiological conditions is vital.
Purpose of the Study:
- To elucidate the structure of bovine respiratory supercomplex I 1III 2IV 1 using cryoelectron microscopy.
- To investigate the role of lipid environments in supercomplex dynamics and function.
Main Methods:
- Cryoelectron microscopy of supercomplexes in a lipid-preserving state.
- Biochemical assays to measure intercomplex quinone transfer activity.
- Structural analysis of conformational changes in complex I.
Main Results:
- Lipid-preserving sample preparation enhanced intercomplex quinone transfer.
- Observed large intercomplex motions creating a dynamic substrate pool between complexes I and III.
- Identified intercomplex phospholipids mediating these motions.
- Discovered a novel channel in complex I for reduced quinone transfer.
Conclusions:
- Supercomplexes utilize dynamic intercomplex movement and a facilitated electron transfer mechanism.
- Phospholipids play a key role in mediating supercomplex dynamics.
- Supercomplexes actively regulate metabolic flux and reactive oxygen species production.
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