Mitochondrial DNA mutations and human disease

Mitochondrial disorders are a group of clinically heterogeneous diseases, commonly defined by a lack of cellular energy due to oxidative phosphorylation (OXPHOS) defects. Since the identification of the first human pathological mitochondrial DNA (mtDNA) mutations in 1988, significant efforts have be...

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Published inBiochimica et biophysica acta Vol. 1797; no. 2; pp. 113 - 128
Main Authors Tuppen, Helen A.L., Blakely, Emma L., Turnbull, Douglass M., Taylor, Robert W.
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 01.02.2010
Subjects
Diagnosis
DNA, Mitochondrial - genetics
Humans
Mitochondrial disease
Mitochondrial Diseases - genetics
Mitochondrial Diseases - pathology
Molecular mechanism
mtDNA
Mutation - genetics
Treatment
L-strand
mtDNA
Molecular mechanism
IMM
H-strand
OXPHOS
2-DE
PGD
Mitochondrial disease
DHU
RC
TCA
Treatment
PD
ROS
Diagnosis
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Summary:Mitochondrial disorders are a group of clinically heterogeneous diseases, commonly defined by a lack of cellular energy due to oxidative phosphorylation (OXPHOS) defects. Since the identification of the first human pathological mitochondrial DNA (mtDNA) mutations in 1988, significant efforts have been spent in cataloguing the vast array of causative genetic defects of these disorders. Currently, more than 250 pathogenic mtDNA mutations have been identified. An ever-increasing number of nuclear DNA mutations are also being reported as the majority of proteins involved in mitochondrial metabolism and maintenance are nuclear-encoded. Understanding the phenotypic diversity and elucidating the molecular mechanisms at the basis of these diseases has however proved challenging. Progress has been hampered by the peculiar features of mitochondrial genetics, an inability to manipulate the mitochondrial genome, and difficulties in obtaining suitable models of disease. In this review, we will first outline the unique features of mitochondrial genetics before detailing the diseases and their genetic causes, focusing specifically on primary mtDNA genetic defects. The functional consequences of mtDNA mutations that have been characterised to date will also be discussed, along with current and potential future diagnostic and therapeutic advances.
Bibliography:ObjectType-Article-2
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ISSN:0005-2728
0006-3002
1879-2650
DOI:10.1016/j.bbabio.2009.09.005