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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Cytopathies involving mitochondrial complex II.

Complex II (succinate-ubiquinone oxidoreductase) is the smallest complex in the respiratory chain and contains four nuclear-encoded subunits SdhA, SdhB, SdhC, and SdhD. It functions both as a respiratory chain component and an essential enzyme of the TCA cycle. Electrons derived from succinate can thus be directly transferred to the ubiquinone pool. Major insights into the workings of complex II have been provided by crystal structures of closely related bacterial enzymes, which have also been genetically manipulated to answer questions of structure-function not approachable using the mammalian system. This information, together with that accrued over the years on bovine complex II and by recent advances in understanding in vivo synthesis of the non-heme iron co-factors of the enzyme, is allowing better recognition of improper functioning of human complex II in diseased states. The discussion in this review is thus limited to cytopathies arising because the enzyme itself is defective or depleted by lack of iron-sulfur clusters. There is a clear dichotomy of effects. Enzyme depletion and mutations in SDHA compromise TCA activity and energy production, whereas mutations in SDHB, SDHC, and SDHD induce paraganglioma. SDHC and SDHD are the first tumor suppressor genes of mitochondrial proteins.[1]

References

  1. Cytopathies involving mitochondrial complex II. Ackrell, B.A. Mol. Aspects Med. (2002) [Pubmed]
 
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