Electron tunneling in respiratory complex I.

Area of Science:

• Biochemistry
• Molecular Biology
• Bioenergetics

Background:

• NADH:ubiquinone oxidoreductase (Complex I) is vital for cellular respiration.
• It couples electron transfer from NADH to ubiquinone with proton gradient generation for ATP synthesis.

Purpose of the Study:

• To elucidate the atomistic details of electronic wiring among Fe/S clusters in Complex I.
• To identify key residues and water molecules involved in electron transfer pathways.

Main Methods:

• Utilized tunneling current theory and computer simulations.
• Employed density functional theory and semiempirical electronic structure methods.
• Analyzed antiferromagnetically coupled spin states and tunneling wave functions.

Main Results:

• Identified distinct electron tunneling pathways between neighboring Fe/S clusters, involving cysteine ligands and key residues.
• Discovered internal water molecules as essential mediators, increasing electron transfer rates by nearly three orders of magnitude.
• Characterized key residues by their sensitivity to mutations and conservation across Complex I homologues.
• Explained the high efficiency of electron transfer by the unique electronic structure of Fe(4)S(4) clusters.

Conclusions:

• The study provides unprecedented atomistic insights into Complex I's electron transfer mechanism.
• Identified specific residues and water mediation critical for efficient energy conversion.
• Highlights the importance of structural and electronic properties for enzyme function in the respiratory chain.