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Respiratory Complex I in Brain Development and Genetic Disease

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Abstract

A study is presented on the expression and activity of complex I, as well as of other complexes of the respiratory chain, in the course of brain development and inherited encephalopathies. Investigations on mouse hippocampal cells show that differentiation of these cells both in vivo and in cell cultures is associated with the expression of a functional complex I, whose activity markedly increases with respect to that of complexes III and IV. Data are presented on genetic defects of complex I in six children with inborn encephalopathy associated with isolated deficiency of the complex. Mutations have been identified in nuclear and mitochondrial genes coding for subunits of the complex. Different mutations were found in the nuclear NDUFS4 gene coding for the 18 kD (IP, AQDQ) subunit of complex I. All the NDUFS4 mutations resulted in impairment of the assembly of a functional complex. The observations presented provide evidence showing a critical role of complex I in differentiation and functional activity of brain cells.

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Authors and Affiliations

  1. Department of Medical Biochemistry and Medical Biology, University of Bari, Bari, Italy

    Sergio Papa, Vittoria Petruzzella, Salvatore Scacco, Rosaria Vergari, Damiano Panelli, Rosanna Tamborra, Margherita Picciariello & Rossana Lambo

  2. Insitute of Biomembranes and Bioenergetics, Italian Research Council, Bari, Italy

    Sergio Papa

  3. Department of Farmacology and Human Physiology, University of Bari, Bari, Italy

    Patrizia Corsi

  4. Molecular Medicine and Neurology, IRCCS-Bambino Gesù, Rome, Italy

    Enrico Bertini & Filippo Maria Santorelli

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  1. Sergio Papa
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  2. Vittoria Petruzzella
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Correspondence to Sergio Papa.

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Papa, S., Petruzzella, V., Scacco, S. et al. Respiratory Complex I in Brain Development and Genetic Disease. Neurochem Res 29, 547–560 (2004). https://doi.org/10.1023/B:NERE.0000014825.42365.16

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