Using cryo-EM to understand the assembly pathway of respiratory complex I

Area of Science:

• Biochemistry
• Structural Biology
• Cell Biology

Background:

• Complex I (proton-pumping NADH:ubiquinone oxidoreductase) is the initial enzyme in the mitochondrial respiratory chain.
• High-resolution cryo-electron microscopy (cryo-EM) has advanced the understanding of Complex I structure and function.
• The biogenesis and assembly factors of Complex I remain less understood structurally.

Purpose of the Study:

• To review current insights into the structural basis of Complex I biogenesis.
• To highlight the role of assembly factors in the intricate process of Complex I formation.
• To discuss the application of cryo-EM in studying Complex I assembly.

Main Methods:

• Review of recent high-resolution cryo-electron microscopy (cryo-EM) studies.
• Analysis of structural data on Complex I and its assembly factors.
• Integration of findings on nuclear and mitochondrial DNA-encoded subunits and assembly factors.

Main Results:

• Cryo-EM has significantly improved the understanding of Complex I structure and function.
• The assembly of Complex I involves over 40 subunits and requires at least 20 distinct assembly factors in humans.
• Limited structural information exists for these crucial assembly factors.

Conclusions:

• Cryo-EM is a powerful tool for elucidating the structural basis of Complex I biogenesis.
• Further structural studies on assembly factors are needed to fully understand Complex I formation.
• This review consolidates recent cryo-EM findings on Complex I assembly pathways.