A Dynamic Substrate Pool Revealed by cryo-EM of a Lipid-Preserved Respiratory Supercomplex
- Authors
- Jeon Tae Jin; Lee Seong-Gyu; Yoo Suk Hyun; Kim Myeongbin; Song Dabin; Ryu Joonghyun; Park Hwangseo; Kim, Deok Soo; Hyun Jaekyung; Kim Ho Min; Ryu, Seong Eon
- Issue Date
- Jun-2022
- Publisher
- MARY ANN LIEBERT, INC
- Keywords
- respiratory supercomplex; lipid-preserving state; cryo-EM structure; dynamic substrate pool; intercomplex movement
- Citation
- ANTIOXIDANTS & REDOX SIGNALING, v.36, no.16-18, pp.1101 - 1118
- Indexed
- SCIE
SCOPUS
- Journal Title
- ANTIOXIDANTS & REDOX SIGNALING
- Volume
- 36
- Number
- 16-18
- Start Page
- 1101
- End Page
- 1118
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/188583
- DOI
- 10.1089/ars.2021.0114
- ISSN
- 1523-0864
- Abstract
- Aims: Mitochondrial respiratory supercomplexes mediate redox electron transfer, generating a proton gradient for ATP synthesis. To provide structural information on the function of supercomplexes in physiologically relevant conditions, we conducted cryoelectron microscopy studies with supercomplexes in a lipid-preserving state.Results: Here, we present cryoelectron microscopy structures of bovine respiratory supercomplex I1III2IV1 by using a lipid-preserving sample preparation. The preparation greatly enhances the intercomplex quinone transfer activity. The structures reveal large intercomplex motions that result in different shapes and sizes of the intercomplex space between complexes I and III, forming a dynamic substrate pool. Biochemical and structural analyses indicated that intercomplex phospholipids mediate the intercomplex motions. An analysis of the different classes of focus-refined complex I showed that structural switches due to quinone reduction led to the formation of a novel channel that could transfer reduced quinones to the intercomplex substrate pool.Innovation and Conclusion: Our results indicate potential mechanism for the facilitated electron transfer involving a dynamic substrate pool and intercomplex movement by which supercomplexes play an active role in the regulation of metabolic flux and reactive oxygen species.
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