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Dysfunction of Mitochondrial Respiratory Chain Complex I in Neurological Disorders: Genetics and Pathogenetic Mechanisms

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Advances in Mitochondrial Medicine

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 942))

Abstract

This chapter covers genetic and biochemical aspects of mitochondrial bioenergetics dysfunction in neurological disorders associated with complex I defects. Complex I formation and functionality in mammalian cells depends on coordinated expression of nuclear and mitochondrial genes, post-translational subunit modifications, mitochondrial import/maturation of nuclear encoded subunits, subunits interaction and stepwise assembly, and on proteolytic processing. Examples of complex I dysfunction are herein presented: homozygous mutations in the nuclear NDUFS1 and NDUFS4 genes for structural components of complex I; an autosomic recessive form of encephalopathy associated with enhanced proteolytic degradation of complex I; familial cases of Parkinson associated to mutations in the PINK1 and Parkin genes, in particular, homoplasmic mutations in the ND5 and ND6 mitochondrial genes of the complex I, coexistent with mutation in the PINK1 gene. This knowledge, besides clarifying molecular aspects of the pathogenesis of hereditary diseases, can also provide hints for understanding the involvement of complex I in neurological disorders, as well as for developing therapeutical strategies

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Acknowledgements

This work was supported by: National Project, “Progetto FIRB Rete Nazionale per lo Studio della Proteomica Umana (Italian Human ProteomeNet)”, 2009, Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR) and University of Bari Research grant, 2009.

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Authors and Affiliations

  1. Department of Basic Medical Sciences, Section of Medical Biochemistry, University of Bari, Policlinico, P.zza G. Cesare, 70124, Bari, Italy

    Vittoria Petruzzella, Anna Maria Sardanelli, Salvatore Scacco, Damiano Panelli, Raffaella Trentadue & Sergio Papa

  2. Institute of Biomembranes and Bioenergetics (IBBE), Italian Research Council, (CNR), Bari, Italy

    Vittoria Petruzzella & Sergio Papa

  3. Department of Dental Sciences and Surgery, University of Bari, Bari, Italy

    Francesco Papa

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  1. Vittoria Petruzzella
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  2. Anna Maria Sardanelli
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  3. Salvatore Scacco
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  4. Damiano Panelli
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  5. Francesco Papa
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Correspondence to Sergio Papa .

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  1. School of Medicine, Institute of Biochemistry and Clinical B, Catholic University, Largo A. Gemelli 8, Rome, 00168, Italy

    Roberto Scatena

  2. School of Medicine, Institute of Biochemistry and Clinical B, Catholic University, Largo A. Gemelli 8, Rome, 00168, Italy

    Patrizia Bottoni

  3. School of Medicine, Institute of Biochemistry and Clinical B, Catholic University, Largo A. Gemelli 8, Rome, 00168, Italy

    Bruno Giardina

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Petruzzella, V. et al. (2012). Dysfunction of Mitochondrial Respiratory Chain Complex I in Neurological Disorders: Genetics and Pathogenetic Mechanisms. In: Scatena, R., Bottoni, P., Giardina, B. (eds) Advances in Mitochondrial Medicine. Advances in Experimental Medicine and Biology, vol 942. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2869-1_17

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