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. 2013 Jul 16;81(3):281-91.
doi: 10.1212/WNL.0b013e31829bfe89.

Mitochondrial encephalomyopathies--fifty years on: the Robert Wartenberg Lecture

Salvatore DiMauro  1
Affiliations

Mitochondrial encephalomyopathies--fifty years on: the Robert Wartenberg Lecture

Salvatore DiMauro. Neurology. .
No abstract available

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Conflict of interest statement

The author reports no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.

Figures

Figure 1
Figure 1. Schematic view of mitochondrial metabolism
The spirals represent the cyclic reactions of the β-oxidation pathway resulting in the formation of acetyl-coenzyme A (CoA) and the reduction of flavoprotein. ADP = adenosine diphosphate; ATP = adenosine triphosphate; ANT = adenine nucleotide translocase; CACT = carnitine-acylcarnitine translocase; CoQ = coenzyme Q; CPT = carnitine palmitoyltransferase; DIC = dicarboxylate carrier; ETF = electron-transfer flavoprotein; ETF-DH = electron-transfer flavoprotein dehydrogenase; FAD = flavin adenine-dinucleotide; FADH = reduced flavin adenine-dinucleotide; NADH = reduced nicotinamide adenine dinucleotide; PDHC = pyruvate dehydrogenase complex; TCA = tricarboxylic acid; I = complex I; II = complex II; III = complex III; IV = complex IV; V = complex V. (Modified with permission from DiMauro and Schon, New England Journal of Medicine 2003;348:2656–2668.)
Figure 2
Figure 2. The respiratory chain (top) and the mitochondrial DNA (bottom)
Genes and corresponding gene products are similarly color-coded. ND denotes the subunits of NADH-coenzyme Q oxidoreductase (complex I); cyt b = cytochrome b; subunits of cytochrome c oxidase are labeled CO in the mtDNA scheme and COX in the respiratory chain rendition; A6 and A8 indicate subunits 6 and 8 of ATP synthase. The 22 tRNA genes are denoted by one-letter amino acid nomenclature; 12S and 16S denote ribosomal RNAs (rRNAs). OH and OL are the origin of heavy- and light-strand replication; HSP and LSP are the promoters of heavy- and light-strand transcription. ADP = adenosine diphosphate; ATP = adenosine triphosphate; IMM = inner mitochondrial membrane; IMS = intermembrane space; MAT = mitochondrial matrix.
Figure 3
Figure 3. Morbidity map of the mitochondrial DNA as of 2013
Disorders caused by mutations in protein-coding genes are shown in red; disorders caused by mutations in genes controlling protein synthesis are shown in blue. FBSN = familial bilateral striatal necrosis; LHON = Leber hereditary optic neuropathy; LS = Leigh syndrome; MELAS = mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes; MERRF = myoclonus epilepsy and ragged-red fibers; MILS = maternally inherited Leigh syndrome; NARP = neuropathy, ataxia, retinitis pigmentosa; PEO = progressive external ophthalmoplegia. (Modified with permission from DiMauro and Schon, New England Journal of Medicine 2003;348:2656-2668.)
Figure 4
Figure 4. Serial cross-sections of a muscle biopsy from a patient with myoclonus epilepsy and ragged-red fibers stained with different histochemical methods
The modified Gomori trichrome shows classic ragged-red fibers, which stain intensely with the succinate dehydrogenase (SDH) stain (“ragged-blue”) and appear pale with the cytochrome c oxidase (COX) stain. The same fibers appear more or less intensely blue when the SDH and COX stain are superimposed.
Figure 5
Figure 5. Serial sections from the brain cortex of a patient with mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes showing COX II immunodeficiency and normal immunoreaction for the FeS protein in pial and intracortical arterioles
(Reprinted with permission from Tanji et al., Semin Cell Dev Biol 2001;12:429-439.)
Figure 6
Figure 6. Schematic representation of the pronuclear transfer technique to prevent transmission of pathogenic mitochondrial DNA point mutations
For explanation, see text.
Figure 7
Figure 7. Six different modalities of mendelian mitochondrial diseases
1, “Direct hits”; 2, “indirect hits”; 3, defects of intergenomic communication resulting in mitochondrial DNA depletion and multiple mitochondrial DNA deletions; 4, defects of mRNA translation; 5, defects of the inner mitochondrial membrane phospholipid milieu; 6, defects of mitochondrial dynamics.
Figure 8
Figure 8. A neuron with mitochondria (stained in red with mitotracker) appended to microtubular “tracks” (stained in green)
Courtesy of Dr. Estela Area-Gómez.
See this image and copyright information in PMC

Comment in

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