"We also demonstrate a physical interaction between human frataxin and human succinate dehydrogenase complex subunits, suggesting also a key role of frataxin in the mitochondrial electron transport chain in humans"

"Biochemical measurement of skeletal muscle showed a severe decrease in mitochondrial complex II. Sequencing of SDHA revealed compound heterozygosity for a nonsense mutation in exon 4 (W119X) and a missense mutation in exon 3 (A83V), both absent in normal controls."

"In six additional patients--five with Leigh or Leigh-like syndrome and one with neuropathy and ataxia associated with isolated deficiency of complex II--mutations in SDHA were not detected, indicating genetic heterogeneity."

"We found that IFN-beta/RA upregulates the expression of MRC complex subunits. Mitochondrial-nuclear translocation of these subunits was not observed, but overproduction of reactive oxygen species (ROS), which causes loss of mitochondrial function, was detected upon IFN-beta/RA treatment."

"Both yeast and human Sdh5 interact with the catalytic subunit of the succinate dehydrogenase (SDH) complex, a component of both the electron transport chain and the tricarboxylic acid cycle. Sdh5 is required for SDH-dependent respiration and for Sdh1 flavination (incorporation of the flavin adenine dinucleotide cofactor)."

"Germline loss-of-function mutations in the human SDH5 gene, located on chromosome 11q13.1, segregate with disease in a family with hereditary paraganglioma, a neuroendocrine tumor previously linked to mutations in genes encoding SDH subunits."

"We confirmed the interaction between TRAP1 and complex II/SDH through further approaches, including (1) immunoprecipitation, finding coimmunoprecipitation (coIP) of TRAP1 with SDH and vice versa (Figure 3C), and (2) mitochondrial protein crosslinking with dimethyl 3,3′-dithiobis-propionimidate (DTBP), a homobifunctional compound that reacts with the primary amines of two interacting proteins at an average distance of about 8 Å (Giorgio et al., 2009), followed by TRAP1 immunoprecipitation in order to determine whether TRAP1 and SDH are closely associated. We found that two TRAP1/SDH complexes are formed in mitochondria (Figure 3D)."

"We found that SQR enzymatic activity was increased in mitochondria from shTRAP1 cells relative to those derived from control cells (Figures 4A, S2A, and S2B). TRAP1 did not affect either the cytochrome oxidase enzymatic activity of complex IV (Figure S2C) or complex II protein levels (Figure S2D) or mitochondrial mass (Figure S2E)."

"We observe that TRAP1-mediated inhibition of SDH limits the maximal rate of respiration and leads to succinate accumulation followed by HIF1α, but not HIF2α, stabilization. Remarkably, the membrane-permeable succinate analog dimethyl succinate could both elicit HIF1α stabilization and rescue the tumorigenic phenotype of shTRAP1 cells, highlighting the mechanistic connection between TRAP1-dependent succinate accumulation and HIF1α-dependent tumor formation."

"A low concentration of the ETC complex II inhibitors 3-nitropropionic acid (3-NP), which inactivates SDH after covalent binding with an Arg residue in the catalytic core of SDHA (Huang et al., 2006), or thenoyltrifluoroacetone (TTFA), which blocks electron transfer from succinate to coenzyme Q at the quinone-binding site in subunits B and D (Huang et al., 2006), inhibited OCR in shTRAP1 cells but were inactive in the presence of TRAP1 (Figures S4B and S4C), paralleling the downmodulation of the SQR activity induced by 3-NP only in TRAP1-expressing mitochondria (Figure 5E)."

"We now report a mutation in the nuclear-encoded flavoprotein (Fp) subunit gene of the succinate dehydrogenase (SDH) in two siblings with complex II deficiency presenting as Leigh syndrome. Both patients were homozygous for an Arg554Trp substitution in the Fp subunit. Their parents (first cousins) were heterozygous for the mutation that occurred in a conserved domain of the protein and was absent from 120 controls."

"The deleterious effect of the Arg to Trp substitution on the catalytic activity of SDH was observed in a SDH- yeast strain transformed with mutant Fp cDNA."

"The Fp subunit gene is duplicated in the human genome (3q29; 5p15), with only the gene on chromosome 5 expressed in human-hamster somatic cell hybrids. This is the first report of a nuclear gene mutation causing a mitochondrial respiratory chain deficiency in humans."

"Complex II (succinate dehydrogenase, SDH) catalyzes the oxidation of succinate to fumarate, coupling two-electron transfer via FAD and iron-sulfur centers to reduce ubiquinone to ubiquinol in the inner mitochondrial membrane"