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Mitochondrial energy metabolism in neurodegeneration associated with methylmalonic acidemia

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Abstract

Methylmalonic acidemia is one of the most prevalent inherited metabolic disorders involving neurological deficits. In vitro experiments, animal model studies and tissue analyses from human patients suggest extensive impairment of mitochondrial energy metabolism in this disease. This review summarizes changes in mitochondrial energy metabolism occurring in methylmalonic acidemia, focusing mainly on the effects of accumulated methylmalonic acid, and gives an overview of the results found in different experimental models. Overall, experiments to date suggest that mitochondrial impairment in this disease occurs through a combination of the inhibition of specific enzymes and transporters, limitation in the availability of substrates for mitochondrial metabolic pathways and oxidative damage.

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Authors and Affiliations

  1. Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, 13083-887, Campinas, SP, Brazil

    Daniela R. Melo & Roger F. Castilho

  2. Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil

    Alicia J. Kowaltowski

  3. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Moacir Wajner

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  1. Daniela R. Melo
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  2. Alicia J. Kowaltowski
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  3. Moacir Wajner
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  4. Roger F. Castilho
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Correspondence to Roger F. Castilho.

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Melo, D.R., Kowaltowski, A.J., Wajner, M. et al. Mitochondrial energy metabolism in neurodegeneration associated with methylmalonic acidemia. J Bioenerg Biomembr 43, 39–46 (2011). https://doi.org/10.1007/s10863-011-9330-2

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