Mitochondrial Respiratory C omplex II

Abstract

The mitochondrial respiratory Complex II, or succinate : ubiquinone oxidoreductase (SQR), is an integral membrane protein complex in both the tricarboxylic acid cycle (Krebs cycle) and aerobic respiration. To date, X‐ray crystal structures of mitochondrial respiratory Complex II have been reported from porcine heart and from chicken, as well as the structures of a number of related bacterial SQR or quinol : fumarate oxidoreductase (QFR) structures. Complex II comprises of two hydrophilic proteins (flavoprotein (Fp) and iron–sulfur protein (Ip)) and two transmembrane proteins (CybL and CybS), as well as prosthetic groups required for electron transfer from succinate to ubiquinone. A proximal ubiquinone site (Qp) is located on the matrix side of the protein complex. Inhibitor‐bound structures using 3‐nitropropionate (NPA), 2‐thenoyltrifluoroacetone (TTFA), and carboxin provide further functional details for Complex II. NPA, a succinate analog, confirms the location of the succinate binding site. TTFA, a classical inhibitor for the ubiquinone reduction of Complex II that works by occupying its ubiquinone binding sites, confirms the location of the Qp site in both porcine heart and chicken structures. The available Complex II structures provide models for studying the mitochondrial respiratory system and human mitochondrial diseases related to mutations in this complex.

Induction of Mitochondrial Cell Death and Reversal of Anticancer Drug Resistance via Nanocarriers Composed of a Triphenylphosphonium Derivative of Tocopheryl Polyethylene Glycol Succinate

“…Also the lengthy polyethylene glycol chain looped conveniently along the contours of the binding site, increasing penetration of the tocopheryl succinate headgroup into the bilayer. The residues Trp-B173, His-B216, Ser-C42, Arg-C46, Tyr-D91, and Asp-D90 are the conserved residues and have been found responsible for their specific substrate binding and catalytic function of the protein CII Figure clearly shows that TPP-TPGS is actively involved in forming H bonding with the Trp B173, His-B216, Tyr-D91, and Asp-D90 which correspond to ubiquinone binding amino acids in the active site of the protein.…”