Complex II

Complex II

Complex II, also known as succinate dehydrogenase (SDH) or succinate-coenzyme Q reductase, is an integral component of the electron transport chain and the citric acid cycle (Krebs cycle) in mitochondria. It plays a crucial role in cellular respiration, facilitating the transfer of electrons from succinate to ubiquinone (coenzyme Q), which is a key step in the production of adenosine triphosphate (ATP).

Structure

Complex II is a multi-subunit enzyme complex embedded in the inner mitochondrial membrane. It consists of four subunits:

• SDHA: The flavoprotein subunit that contains the active site for succinate oxidation. It binds flavin adenine dinucleotide (FAD) as a prosthetic group.
• SDHB: The iron-sulfur protein subunit that contains three iron-sulfur clusters ([2Fe-2S], [4Fe-4S], and [3Fe-4S]) that facilitate electron transfer.
• SDHC and SDHD: These are the membrane-anchoring subunits that bind to ubiquinone and help anchor the complex to the inner mitochondrial membrane.

Function

Complex II catalyzes the oxidation of succinate to fumarate in the citric acid cycle, while simultaneously reducing ubiquinone to ubiquinol in the electron transport chain. The reaction can be summarized as follows:

Succinate + FAD → Fumarate + FADH₂

FADH₂ + Ubiquinone → FAD + Ubiquinol

This process does not directly contribute to the proton gradient across the mitochondrial membrane, unlike other complexes in the electron transport chain, but it is essential for the continuation of the citric acid cycle and the overall process of oxidative phosphorylation.

Clinical Significance

Mutations in the genes encoding the subunits of Complex II can lead to a variety of diseases, including certain types of cancer and mitochondrial disorders. For example, mutations in SDHB, SDHC, and SDHD are associated with hereditary paraganglioma and pheochromocytoma, which are tumors of the nervous system.

Research and Applications

Complex II is a target for various research studies aiming to understand its role in metabolism and disease. Inhibitors of Complex II, such as malonate, are used in research to study metabolic pathways and the effects of impaired electron transport.

Also see

• Electron transport chain
• Citric acid cycle
• Mitochondria
• Oxidative phosphorylation
• Ubiquinone