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Structure paper

TitleStructural basis of mitochondrial membrane bending by the I-II-III-IV supercomplex.
Journal, issue, pagesNature, Vol. 615, Issue 7954, Page 934-938, Year 2023
Publish dateMar 22, 2023
AuthorsAlexander Mühleip / Rasmus Kock Flygaard / Rozbeh Baradaran / Outi Haapanen / Thomas Gruhl / Victor Tobiasson / Amandine Maréchal / Vivek Sharma / Alexey Amunts /
PubMed AbstractMitochondrial energy conversion requires an intricate architecture of the inner mitochondrial membrane. Here we show that a supercomplex containing all four respiratory chain components contributes ...Mitochondrial energy conversion requires an intricate architecture of the inner mitochondrial membrane. Here we show that a supercomplex containing all four respiratory chain components contributes to membrane curvature induction in ciliates. We report cryo-electron microscopy and cryo-tomography structures of the supercomplex that comprises 150 different proteins and 311 bound lipids, forming a stable 5.8-MDa assembly. Owing to subunit acquisition and extension, complex I associates with a complex IV dimer, generating a wedge-shaped gap that serves as a binding site for complex II. Together with a tilted complex III dimer association, it results in a curved membrane region. Using molecular dynamics simulations, we demonstrate that the divergent supercomplex actively contributes to the membrane curvature induction and tubulation of cristae. Our findings highlight how the evolution of protein subunits of respiratory complexes has led to the I-II-III-IV supercomplex that contributes to the shaping of the bioenergetic membrane, thereby enabling its functional specialization.
External linksNature / PubMed:36949187 / PubMed Central
MethodsEM (single particle) / EM (subtomogram averaging)
Resolution2.6 - 28.0 Å
Structure data

15865

8b6f

EMDB-15865, PDB-8b6f:
Cryo-EM structure of NADH:ubiquinone oxidoreductase (complex-I) from respiratory supercomplex of Tetrahymena thermophila
Method: EM (single particle) / Resolution: 2.8 Å

15866

8b6g

EMDB-15866, PDB-8b6g:
Cryo-EM structure of succinate dehydrogenase complex (complex-II) in respiratory supercomplex of Tetrahymena thermophila
Method: EM (single particle) / Resolution: 3.0 Å

15867

8b6h

EMDB-15867, PDB-8b6h:
Cryo-EM structure of cytochrome c oxidase dimer (complex IV) from respiratory supercomplex of Tetrahymena thermophila
Method: EM (single particle) / Resolution: 2.6 Å

15868

8b6j

EMDB-15868, PDB-8b6j:
Cryo-EM structure of cytochrome bc1 complex (complex-III) from respiratory supercomplex of Tetrahymena thermophila
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-15900: Subtomogram average of the respiratory supercomplex from Tetrahymena thermophila mitochondria
Method: EM (subtomogram averaging) / Resolution: 28.0 Å

Chemicals

ChemComp-CDL:
CARDIOLIPIN / phospholipid*YM / Cardiolipin

ChemComp-UDP:
URIDINE-5'-DIPHOSPHATE / UDP*YM / Uridine diphosphate

ChemComp-MG:
Unknown entry

ChemComp-PC1:
1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE / phospholipid*YM / Phosphatidylcholine

ChemComp-NDP:
NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / Nicotinamide adenine dinucleotide phosphate

ChemComp-3PE:
1,2-Distearoyl-sn-glycerophosphoethanolamine / phospholipid*YM / Phosphatidylethanolamine

ChemComp-LPP:
2-(HEXADECANOYLOXY)-1-[(PHOSPHONOOXY)METHYL]ETHYL HEXADECANOATE / phospholipid*YM

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM / Adenosine diphosphate

ChemComp-FES:
FE2/S2 (INORGANIC) CLUSTER / Iron–sulfur cluster

ChemComp-SF4:
IRON/SULFUR CLUSTER / Iron–sulfur cluster

ChemComp-FMN:
FLAVIN MONONUCLEOTIDE / Flavin mononucleotide

ChemComp-8Q1:
S-[2-({N-[(2R)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)butanoyl]-beta-alanyl}amino)ethyl] dodecanethioate

ChemComp-ZN:
Unknown entry

ChemComp-CA:
Unknown entry

ChemComp-FAD:
FLAVIN-ADENINE DINUCLEOTIDE / FAD*YM / Flavin adenine dinucleotide

ChemComp-F3S:
FE3-S4 CLUSTER / Iron–sulfur cluster

ChemComp-HEC:
HEME C / Heme C

ChemComp-UQ8:
Ubiquinone-8

ChemComp-HEA:
HEME-A / Heme A

ChemComp-CU:
COPPER (II) ION / Copper

ChemComp-CUA:
DINUCLEAR COPPER ION

ChemComp-K:
Unknown entry

ChemComp-HEM:
PROTOPORPHYRIN IX CONTAINING FE / Heme B

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM / Adenosine triphosphate

ChemComp-PEE:
1,2-dioleoyl-sn-glycero-3-phosphoethanolamine / DOPE, phospholipid*YM / Discrete optimized protein energy

Source
  • tetrahymena thermophila (eukaryote)
  • tetrahymena thermophila sb210 (eukaryote)
KeywordsELECTRON TRANSPORT / Ciliate / mitochondrial / complex-I / supercomplex / Complex-II / cytochrome bc1

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