Abstract
Mitochondrial diseases are uniquely interesting from a genetic point of view because mitochondria contain their own DNA (mtDNA) and are capable of synthesizing a small but vital set of proteins, all of which are components of respiratory chain complexes. Numerous mutations in mtDNA have been described in the past 5 years, and, it is, therefore, important for the clinician to keep in mind both some characteristic clinical presentations and, more importantly, some basic principles of 'mitochondrial genetics,' including heteroplasmy, the threshold effect, mitotic segregation, and maternal inheritance. The vast majority of mitochondrial proteins are encoded by nuclear DNA (nDNA) and have to be imported from the cytoplasm into mitochondria through a complex translocation machinery, which is also under the control of the nuclear genome. In addition, nDNA encodes several factors that control mtDNA replication, transcription, and translocation. Mitochondrial diseases due to mutations in nDNA are transmitted as mendelian traits and fall into three categories: (1) alterations of mitochondrial proteins; (2) alterations of mitochondrial protein importation; and (3) alterations of intergenomic communication. The first group of disorders can be further classified on the basis of the biochemical area affected, including defects of transport, defects of substrate utilization, defects of the Krebs cycle, defects of oxidation/phosphorylation coupling, and defects of the respiratory chain. The second group includes only few well-documented disorders but will certainly expand in the near future. The third group includes two conditions, an autosomal dominant form of progressive external ophthalmoplegia associated with multiple mtDNA deletions, and a quantitative defect of mtDNA (mtDNA depletion) causing severe infantile myopathy or hepatopathy.
| Original language | English |
|---|---|
| Pages (from-to) | 1197-1208 |
| Number of pages | 12 |
| Journal | Archives of Neurology |
| Volume | 50 |
| Issue number | 11 |
| State | Published - Nov 19 1993 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Mitochondrial encephalomyopathies. / DiMauro, S.; Moraes, Carlos T.
In: Archives of Neurology, Vol. 50, No. 11, 19.11.1993, p. 1197-1208.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mitochondrial encephalomyopathies
AU - DiMauro, S.
AU - Moraes, Carlos T
PY - 1993/11/19
Y1 - 1993/11/19
N2 - Mitochondrial diseases are uniquely interesting from a genetic point of view because mitochondria contain their own DNA (mtDNA) and are capable of synthesizing a small but vital set of proteins, all of which are components of respiratory chain complexes. Numerous mutations in mtDNA have been described in the past 5 years, and, it is, therefore, important for the clinician to keep in mind both some characteristic clinical presentations and, more importantly, some basic principles of 'mitochondrial genetics,' including heteroplasmy, the threshold effect, mitotic segregation, and maternal inheritance. The vast majority of mitochondrial proteins are encoded by nuclear DNA (nDNA) and have to be imported from the cytoplasm into mitochondria through a complex translocation machinery, which is also under the control of the nuclear genome. In addition, nDNA encodes several factors that control mtDNA replication, transcription, and translocation. Mitochondrial diseases due to mutations in nDNA are transmitted as mendelian traits and fall into three categories: (1) alterations of mitochondrial proteins; (2) alterations of mitochondrial protein importation; and (3) alterations of intergenomic communication. The first group of disorders can be further classified on the basis of the biochemical area affected, including defects of transport, defects of substrate utilization, defects of the Krebs cycle, defects of oxidation/phosphorylation coupling, and defects of the respiratory chain. The second group includes only few well-documented disorders but will certainly expand in the near future. The third group includes two conditions, an autosomal dominant form of progressive external ophthalmoplegia associated with multiple mtDNA deletions, and a quantitative defect of mtDNA (mtDNA depletion) causing severe infantile myopathy or hepatopathy.
AB - Mitochondrial diseases are uniquely interesting from a genetic point of view because mitochondria contain their own DNA (mtDNA) and are capable of synthesizing a small but vital set of proteins, all of which are components of respiratory chain complexes. Numerous mutations in mtDNA have been described in the past 5 years, and, it is, therefore, important for the clinician to keep in mind both some characteristic clinical presentations and, more importantly, some basic principles of 'mitochondrial genetics,' including heteroplasmy, the threshold effect, mitotic segregation, and maternal inheritance. The vast majority of mitochondrial proteins are encoded by nuclear DNA (nDNA) and have to be imported from the cytoplasm into mitochondria through a complex translocation machinery, which is also under the control of the nuclear genome. In addition, nDNA encodes several factors that control mtDNA replication, transcription, and translocation. Mitochondrial diseases due to mutations in nDNA are transmitted as mendelian traits and fall into three categories: (1) alterations of mitochondrial proteins; (2) alterations of mitochondrial protein importation; and (3) alterations of intergenomic communication. The first group of disorders can be further classified on the basis of the biochemical area affected, including defects of transport, defects of substrate utilization, defects of the Krebs cycle, defects of oxidation/phosphorylation coupling, and defects of the respiratory chain. The second group includes only few well-documented disorders but will certainly expand in the near future. The third group includes two conditions, an autosomal dominant form of progressive external ophthalmoplegia associated with multiple mtDNA deletions, and a quantitative defect of mtDNA (mtDNA depletion) causing severe infantile myopathy or hepatopathy.
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UR - http://www.scopus.com/inward/citedby.url?scp=0027525492&partnerID=8YFLogxK
M3 - Article
C2 - 8215979
AN - SCOPUS:0027525492
VL - 50
SP - 1197
EP - 1208
JO - Archives of Neurology
JF - Archives of Neurology
SN - 0003-9942
IS - 11
ER -