Structural organization of the gene encoding the human iron-sulfur subunit of succinate dehydrogenase

Au, Harry C.; Ream-Robinson, Deena; Bellew, Liz Anne; Broomfield, P. L. E.; Saghbini, Michael; Scheffler, Immo E.

doi:10.1016/0378-1119(95)00162-y

Cited by 53 publications

(33 citation statements)

References 13 publications

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“…Although it is bound to the inner mitochondrial membrane, it is encoded entirely in the nucleus (34). An examination of fibroblasts established from donors of different ages revealed that fetal lines exhibited a significantly lower mRNA abundance than adults (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We also determined the mRNA abundances of representative sets of nuclear and mitochon-drial encoded subunits of ND and COX in these lines. Additionally, we determined the mRNA abundance of succinate dehydrogenase (SD), which is encoded entirely by the nuclear genome (33,34) for a comparison with the nuclear encoded subunits of the mosaic enzymes examined. We have determined previously that the skin fibroblast model, used in this study, maintains the development and age-dependent differences in antioxidant defenses known to exist in numerous organisms and tissues in vivo (22)(23)(24).…”

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confidence: 99%

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Development and Age-associated Differences in Electron Transport Potential and Consequences for Oxidant Generation

Allen

Keogh²,

Tresini

et al. 1997

Journal of Biological Chemistry

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We determined the activities of NADH dehydrogenase (ND), succinate dehydrogenase, and cytochrome c oxidase (COX) in 29 skin fibroblast lines established from donors ranging in age from 12 gestational weeks to 94 years. The results of this study demonstrate that all three of the enzyme activities examined are greater in adult-derived fibroblasts than in the fetal cell lines. The ratio of enzyme activities that control electron entry into and exit from the electron transport chain varied directly with lucigenin-detected chemiluminescence (an indicator of ⅐ O 2 ؊ generation) and inversely with H 2 O 2 generation. These results indicate a clear difference in the predominant oxidant species generated during fetal and adult stages of life. We also examined the mRNA abundances of different components of the electron transport chain complexes. We observed higher abundances of mitochondrial encoded mRNAs (COX 1 and ND 4) in cell lines established from adults than in fetal cells. No differences in the mRNA abundances of the nuclear encoded sequences (COX 4 and ND 51) were observed in fetal and postnatal-derived lines. Succinate dehydrogenase mRNA abundance was greater in cell lines established from postnatal donors than in fetal cell lines. No significant differences between cell lines established from young and old adults were detected in any of the parameters examined.Mitochondria are the primary site of aerobic energy production and are thus the major site of generation of reactive oxygen species (ROS), 1 such as oxygen-centered free radicals and peroxides, which are by-products of metabolism (1-4). Estimates of the rate of ROS generation can differ greatly; however, it has been demonstrated repeatedly that the relative rate of oxidant generation increases with age and that this increase correlates strongly with age-associated changes in the cellular redox state (5-8). For example, the rates of superoxide ( ⅐ O 2 Ϫ ) (8 -14) and H 2 O 2 generation (7, 10, 14 -17) increase in the cells of aging organisms, whereas the glutathione concentration declines progressively with advancing age (5,6,18,19). Differences in ROS metabolism also exist between cells obtained from early developmental stages and from postnatal tissues (for review, see Refs. 20 and 21). The activities of enzymic antioxidant defenses tend to be lower in fetal cells than in cells derived from postnatal tissues (22-24); however, the GSH concentration is frequently greater in fetal cells than in cells from adults (20,24). Whether these observations reflect differences in the steadystate level of ROS in fetal and postnatal cells is not presently known (20, 21).The rate of mitochondrial ROS generation in cells is largely dependent on the amounts of autoxidizable respiratory carriers and the redox state of electron carriers (1,3,25,26). All electron carriers located prior to one of low abundance will exhibit a greater propensity to be chemically reduced because of the slowing of electron flux (electron stacking; 1, 16, 25, 27). Thus, either age or development-a...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Development and Age-associated Differences in Electron Transport Potential and Consequences for Oxidant Generation

Allen

Keogh²,

Tresini

et al. 1997

Journal of Biological Chemistry

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“…A DNA oligomer containing the NRF-1 core sequence forms a sponsive element (IRE) in its 5′UTR (Gray et al, 1996;Melefors, 1996;Kohler et al, 1995). The 5′UTR is extremely DNA-protein complex with the NRF-1 transcriptional activator from HeLa nuclear extract (Fig.…”

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confidence: 99%

“…sophila SDH2 transcript (Gray et al, 1996;Melefors, 1996;Kohler et al, 1995), but it was not possible to establish such a The NRF-1 core sequence found in the SDH2 promoter (TGgGCATGCGCc) differed slightly from the consensus core role for the human IRE-like sequence (Melefors, 1996).…”

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confidence: 99%

Promoter analysis of the human succinate dehydrogenase iron‐protein gene

Scheffler

1998

European Journal of Biochemistry

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The iron-sulfur subunit of succinate dehydrogenase is one of the four subunits of complex II of the mitochondrial electron transport chain. Its gene, SDH2, is one of the four nuclear-encoded genes for this complex. Reporter gene analysis of the human SDH2 promoter indicates that it is transcriptionally regulated by the nuclear respiratory factors NRF-1 and NRF-2. Their binding sites reside immediately upstream (within 90 bp) of the transcription start site. Site-directed mutagenesis of either site lowers the reporter gene activity by tenfold to a basal level. Gel shift experiments and competition experiments with the authentic NRF-1 and NRF-2 DNA oligomers from previously characterized nuclear respiratory genes strengthen the proposed role of these two transcriptional regulators. These experiments extend the proposed regulatory role of these two transcription factors to complex II of the respiratory chain.The expression of three of the four genes of complex II was also examined when mouse myoblast C2C12 cells were induced to differentiate into myotubes. Up-regulation upon differentiation in tissue culture is only modest, 2Ϫ3 fold over the myoblast cells.

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“…SDHB is one of four protein subunits forming SDH, the others being SDHA, SDHC and SDHD. Germline mutations in SDH proteins can cause familial paraganglioma [1]. SDHB along with SDHC and SDHD are tumour suppressor genes.…”

Section: Introductionmentioning

confidence: 99%

Cardiac Paraganglioma associated with SDHB mutation and elevated 3-methoxytyramine levels

Jones¹,

Barwell²,

Bhake³

et al. 2017

EJEA

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Structural organization of the gene encoding the human iron-sulfur subunit of succinate dehydrogenase

Cited by 53 publications

References 13 publications

Development and Age-associated Differences in Electron Transport Potential and Consequences for Oxidant Generation

Development and Age-associated Differences in Electron Transport Potential and Consequences for Oxidant Generation

Promoter analysis of the human succinate dehydrogenase iron‐protein gene

Cardiac Paraganglioma associated with SDHB mutation and elevated 3-methoxytyramine levels

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