ISSN:
1573-6881
Keywords:
Mitochondrial DNA
;
oxidative phosphorylation
;
human disease
;
base substitutions
;
rearrangements
;
genotype
;
phenotype
;
missense
;
transfer RNA
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Physics
Notes:
Abstract Mitochondrial ATP production via oxidative phosphorylation (OXPHOS) is essential for normal function and maintenance of human organ systems. Since OXPHOS biogenesis depends on both nuclear- and mitochondrial-encoded gene products, mutations in both genomes can result in impaired electron transport and ATP synthesis, thus causing tissue dysfunction and, ultimately, human disease. Over 30 mitochondrial DNA (mtDNA) point mutations and over 100mtDNA rearrangements have now been identified as etiological factors in human disease. Because of the unique characteristics of mtDNA genetics, genotype/phenotype associations are often complex and disease expression can be influenced by a number of factors, including the presence of nuclear modifying or susceptibility alleles. Accordingly, these mutations result in an extraordinarily broad spectrum of clinical phenotypes ranging from systemic, lethal pediatric disease to late-onset, tissue-specific neurodegenerative disorders. In spite of its complexity, an understanding of the molecular basis of mitochondrial DNA disease will be essential as the first step toward rationale and permanent curative therapy.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00763099
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