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Mitochondrial Respiratory Chain Complex II

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Mitochondrial Disorders Caused by Nuclear Genes

Abstract

Mitochondrial succinate dehydrogenase (SDH), complex II, is an important component of both the mitochondrial respiratory chain and the Krebs cycle. This is the only one of the mitochondrial respiratory chain complexes that is completely encoded by nuclear genes; SDHA, B, C, and D. Recently, two nuclear-encoded assembly factors SDHFA1 and 2 have been identified. Mutations in all four subunit genes and the two assembly factors have now been reported. SDHA and SDHFA1 mutations primarily cause encephalomyopathy in childhood while mutations in the other three subunits and SDHFA2 have been associated with tumor formation. SDH oxidizes succinate as part of the Krebs cycle and in tandem effects the transfer of electrons to ubiquinone. Mutations affecting the former function appear to result in encephalomyelopathy, while mutations affecting electron transfer within the complex appear to result in tumor formation. The dual role of SDH thus appears to account for the major differences in the phenotypes associated with SDH deficiency. This chapter explores the structure and function of the different subunits of SDH, their role in mitochondrial function, and how their dysfunction results in disease. Identifying SDH mutations as important underlying causes of disease enables genetic counseling, early diagnosis, and management of at risk relatives.

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Acknowledgements

To all the patients and their families who inspire us every day.

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Authors and Affiliations

  1. Clinical Pediatrics, Section of Metabolic Diseases, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Jaya Ganesh M.D.

  2. Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, NAB 2015, 77030, Houston, TX, USA

    Lee-Jun C. Wong Ph.D. & Elizabeth B. Gorman Ph.D.

Authors
  1. Jaya Ganesh M.D.
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  2. Lee-Jun C. Wong Ph.D.
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  3. Elizabeth B. Gorman Ph.D.
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Corresponding author

Correspondence to Elizabeth B. Gorman Ph.D. .

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Editors and Affiliations

  1. , Dept. of Molecular and Human Genetics, Baylor College of Medicine, Baylor Plaza ONE, Houston, 77030, Texas, USA

    Lee-Jun C. Wong

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Ganesh, J., Wong, LJ., Gorman, E. (2013). Mitochondrial Respiratory Chain Complex II. In: Wong, LJ. (eds) Mitochondrial Disorders Caused by Nuclear Genes. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3722-2_13

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