Mitochondrial energy metabolism in neurodegeneration associated with methylmalonic acidemia

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.

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)

FINEP Rede Instituto Brasileiro de Neurociencia (IBN-Net)

Financiadora de Estudos e Projetos (FINEP)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)

Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS)

Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS)

National Institutes of Health (NIH)

National Institutes of Health (NIH)

Institutos Nacionais de Ciencia e Tecnologia (INCT/MCT/CNPq)

Institutos Nacionais de Ciencia e Tecnologia (INCT/MCT/CNPq)