Investigations of the mechanism of mitochondrial complex I by electron cryomicroscopy

Mitochondria are double membrane-bound organelles found in the cytosol of eukaryotic cells. They generate energy for the cell by oxidising the breakdown products of metabolism and relaying the liberated electrons through a series of membrane-embedded oxidoreductase proteins known as the electron transport chain (ETC). The first enzyme in the ETC is complex I (NADH:ubiquinone oxidoreductase). Complex I oxidises NADH in the matrix, reduces ubiquinone in the inner membrane, and couples the energy released to the translocation of four protons across the inner membrane, generating the proton motive force that powers vital cellular processes. The major question of how the energy liberated by NADH:ubiquinone oxidoreduction is captured and efficiently exploited to drive proton translocation is still unanswered. Addressing this question is important for understanding clinically relevant complex I dysfunctions and for pharmacological manipulation of the enzyme. The projects presented here aimed to investigate the mechanism of complex I by using single-particle electron cryomicroscopy (cryo-EM) to generate three-dimensional reconstructions of its structure.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2020

Author dc:creator

• Grba, Daniel

Advisor dc:contributor.advisor

• Hirst, Judy

• NADH:ubiquinone oxidoreductase
• Mitochondria
• Structural biology
• Yarrowia lipolytica
• Membrane protein
• Electron cryomicroscopy
• Complex I
• Acetogenin
• Proton translocation

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/aef5e5fd-5a12-47ce-92c9-cdc0b8c34e1f/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

eng

Author Identifier

0000-0003-2915-951X
0000-0001-8667-6797

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/317964