Complex I, also known as NADH:ubiquinone oxidoreductase or NADH dehydrogenase, is the first critical component of the electron transport chain (ETC) in oxidative phosphorylation. It is the first and largest protein complex in the ETC and plays a central role in generating ATP. Complex I acts as a redox-driven proton pump, catalysing the transfer of electrons from NADH to ubiquinone (Q), whilst simultaneously pumping protons across the inner mitochondrial membrane to establish a proton gradient. The primary function of Complex I is to accept electrons from NADH, a reduced form of nicotinamide adenine dinucleotide, and transfer them to ubiquinone (Q), a mobile electron carrier within the inner mitochondrial membrane. The transfer of electrons through the complex occurs in a series of redox reactions, involving a series of iron-sulphur (Fe-S) clusters and flavin mononucleotide (FMN) cofactors. The process begins with the binding of NADH to the flavin mononucleotide (FMN) site in Complex I. NADH donates two electrons and two protons to FMN, forming FMNH2 (reduced FMN). The electrons are then transferred from FMNH2 to a series of iron-sulphur clusters (Fe-S) within Complex I. Finally, the electrons are transferred to ubiquinone (Q), reducing it to ubiquinol (QH2). As electrons pass through Complex I and transfer from NADH to ubiquinone, protons are simultaneously pumped across the inner mitochondrial membrane from the matrix to the intermembrane space. This process is driven by the redox reactions and protein conformational changes that occur during electron transfer. The pumping of protons creates an electrochemical proton gradient, with a higher concentration of protons in the intermembrane space compared to the matrix. This proton gradient is crucial for ATP synthesis and is used by ATP synthase, Complex V, to drive the ATP synthesis. Complex I is highly regulated to ensure efficient electron flow and prevent the generation of reactive oxygen species (ROS), harmful by-products of electron transport that can damage cellular components, including DNA, proteins, and lipids. To prevent excessive ROS production, Complex I is subject to regulatory mechanisms that can either slow down or halt electron flow under certain conditions. One such regulatory mechanism involves the reversible dissociation of the iron - sulphur cluster N2 from the complex, known as the iron-sulphur switch. This switch helps to redirect electron flow away from Complex I and prevent the build-up of electrons, reducing the potential for ROS generation. Complex I dysfunction has been implicated in various human diseases, including mitochondrial disorders, neurodegenerative diseases, and aging-related conditions. Mutations in genes encoding subunits of Complex I, or in assembly factors, can lead to impaired electron transfer and reduced ATP production. Symptoms of complex 1 deficiency can vary widely and may include neurological issues, muscle weakness, developmental delays, and metabolic abnormalities. Finally, defects in Complex I have been associated with the overproduction of ROS and oxidative stress, contributing to cellular damage and disease pathogenesis. Explore our full Complex I product range below and discover more, for less.