High impact information on SDH4

• One b-type heme and two ubiquinone or inhibitor analog molecules were docked into the Sdh3p and Sdh4p membrane dimer [1].
• We analyzed three point mutations (F69V, S71A, and H99L) and one nonsense mutation (Y89OCH) that truncates the Sdh4p subunit at the third predicted transmembrane segment [2].
• Using a random mutagenesis approach, we identified functionally important amino acid residues in one of the anchor subunits, Sdh4p [2].
• The carboxyl terminus of the Saccharomyces cerevisiae succinate dehydrogenase membrane subunit, SDH4p, is necessary for ubiquinone reduction and enzyme stability [3].
• Isolation and characterization of the Saccharomyces cerevisiae SDH4 gene encoding a membrane anchor subunit of succinate dehydrogenase [4].

Biological context of SDH4

• We have previously identified four genes, ACN8, ACN9, ACN17, and ACN18, whose mutant phenotype includes two- to fourfold elevated levels of enzymes of the glyoxylate cycle, gluconeogenesis, and acetyl-CoA metabolism [5].

Anatomical context of SDH4

• They are anchored to the inner mitochondrial membrane by two small, hydrophobic subunits, SDH3p and SDH4p, which are required for electron transfer and ubiquinone reduction [3].
• The cytochrome is not detectable in mitochondria isolated from SDH3 and SDH4 deletion strains [6].

Associations of SDH4 with chemical compounds

• We have constructed an SDH4 mutant by targeted gene disruption; it retains the ability to grow on rich glycerol medium [4].
• We systematically mutated all the histidine and cysteine residues in Sdh3p and Sdh4p to identify the residues involved in axial heme ligation [7].

Other interactions of SDH4

• The membrane intrinsic domain, consisting of Sdh3p and Sdh4p, is proposed to bind two molecules of ubiquinone and one heme [8].
• The yeast succinate dehydrogenase (SDH) is a tetramer of non-equivalent subunits, Sdh1p-Sdh4p, that couples the oxidation of succinate to the transfer of electrons to ubiquinone [9].

Analytical, diagnostic and therapeutic context of SDH4

• Five Lys-132 substituted SDH4 genes were constructed by site-directed mutagenesis and introduced into an SDH4 knockout strain [9].
• Western blot analysis of SDH4 disruption mutant membrane fractions indicates that membrane attachment of the flavoprotein and iron-sulfur subunits is impaired but not abolished [4].

References