Structure of mammalian respiratory complex I

Area of Science:

• Biochemistry
• Structural Biology
• Mitochondrial Biology

Background:

• Complex I (NADH:ubiquinone oxidoreductase) is crucial for ATP synthesis in mammalian mitochondria.
• It comprises 14 conserved core subunits and 31 mammalian-specific supernumerary subunits.
• The functions of supernumerary subunits are not well understood.

Purpose of the Study:

• To determine the complete structure of mammalian Complex I.
• To elucidate the roles of supernumerary subunits.
• To understand Complex I's dynamic transitions and regulation.

Main Methods:

• Single-particle electron cryomicroscopy (cryo-EM) at 4.2 Å resolution.
• Computational sorting of structural classes.
• Modeling of all 45 subunits.

Main Results:

• The complete 45-subunit structure of Bos taurus Complex I was determined.
• All 31 supernumerary subunits were located and modeled.
• Structural dynamics related to the active-to-de-active transition were identified.

Conclusions:

• The study provides a foundational structure for understanding Complex I assembly and dysfunction.
• Insights into the roles of supernumerary subunits and catalytic regulation are revealed.
• The findings offer a basis for studying Complex I-related diseases.