Mitochondrial respiratory dysfunction and mutations in mitochondrial DNA in PINK1 familial Parkinsonism |
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Authors: | Sergio Papa Anna Maria Sardanelli Nazzareno Capitanio Claudia Piccoli |
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Institution: | (1) Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240 Shanghai, China;(2) College of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240 Shanghai, China; |
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Abstract: | A summary is presented of the cellular function and topology of the protein products of genes whose mutations are associated
with familial forms of Parkinsonism, with particular emphasis on mitochondrial involvement. Observations are reviewed which
show mitochondrial respiratory depression in the fibroblasts of a patient affected by familial Parkinsomism associated with
homozygous PINK1 mutation. The respiratory depression, which was due to loss of mitochondrial cytochrome c, was associated
with decreased capacity of respiratory chain oxidative phosphorylation and enhanced cellular level of ROS. Sequence analysis
of the overall mtDNA revealed coexistence with the PINK1 mutation of homoplasmic point mutations in the ND5 and ND6 genes
of complex I. The presence of these mutations appears to have an impact on the development of the Parkinsonism, which can
also occur in the heterozygous PINK1 mutation state. |
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Keywords: | |
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