[34] MtDNA-encoded histocompatibility antigens

Dabhi, Vikram M.; Lindahl, Kirsten Fischer

doi:10.1016/0076-6879(95)60159-7

Cited by 22 publications

(18 citation statements)

References 54 publications

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“…However, LHON mtDNA mutations also sensitize cells to apoptotic cell death, perhaps exposing neurons to the downstream consequences of an inflammatory insult. There is also evidence that mtDNA codes for a maternally inherited human leukocyte antigen, 23 and that mtDNA itself can be proinflammatory if released into the circulation. It is therefore possible that the underlying sequence variations themselves modify the inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Clinical features of MS associated with Leber hereditary optic neuropathy mtDNA mutations

et al. 2013

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Objective:To determine whether the association between multiple sclerosis (MS) and Leber hereditary optic neuropathy (LHON) (known as “Harding disease”) is a chance finding, or the 2 disorders are mechanistically linked.Methods:We performed a United Kingdom–wide prospective cohort study of prevalent cases of MS with LHON mitochondrial DNA (mtDNA) mutations. The new cases were compared with published cases, enabling a comprehensive clinical description. We also performed a meta-analysis of studies screening patients with MS for LHON mtDNA mutations to find evidence of a genetic association.Results:Twelve new patients were identified from 11 pedigrees, and 44 cases were identified in the literature. The combined cohort had the following characteristics: multiple episodes of visual loss, predominance for women, and lengthy time interval before the fellow eye is affected (average 1.66 years), which is very atypical of LHON; conversely, most patients presented without eye pain and had a poor visual prognosis, which is unusual for optic neuritis associated with MS. The number of UK cases of LHON-MS fell well within the range predicted by the chance occurrence of MS and the mtDNA mutations known to cause LHON. There was no association between LHON mtDNA mutations and MS in a meta-analysis of the published data.Conclusions:Although the co-occurrence of MS and LHON mtDNA mutations is likely to be due to chance, the resulting disorder has a distinct phenotype, implicating a mechanistic interaction. Patients with LHON-MS have a more aggressive course, and prognostication and treatment should be guarded.

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Section: Discussionmentioning

confidence: 99%

Clinical features of MS associated with Leber hereditary optic neuropathy mtDNA mutations

et al. 2013

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“…Each of the mitochondrially encoded respiratory-chain subunits of Saccharomyces cerevisiae contains at least one hydrophilic tail or loop that is exported to the outside surface of the inner membrane by translocation across the lipid bilayer (48). In addition to their important role in assembly of the respiratory complexes, mitochondrial export translocation systems might play a role in transporting mitochondrially encoded polypeptides out of the organelle in animal (9) and plant (1) cells. Export systems also could be involved in intracellular signaling by mitochondria (31) and possibly, by analogy to whole cells (4,50), in removal of toxic components from the organelle.…”

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confidence: 99%

Mutations Affecting a Yeast Mitochondrial Inner Membrane Protein, Pnt1p, Block Export of a Mitochondrially Synthesized Fusion Protein from the Matrix

Fox

1999

Molecular and Cellular Biology

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The machinery that inserts mitochondrially encoded proteins into the inner membrane and translocates their hydrophilic domains through the membrane is poorly understood. We have developed a genetic screen for Saccharomyces cerevisiae mutants defective in this export process. Here we show that mutations in the nuclear gene PNT1 block the translocation of mitochondrially encoded fusion proteins across the inner membrane. Pnt1p is a mitochondrial integral inner membrane protein that appears to have two hydrophilic domains in the matrix, flanking a central hydrophobic hairpin-like anchor. While an S. cerevisiae pnt1 deletion mutant was more sensitive to H 2 O 2 than the wild type was, it was respiration competent and able to export wild-type Cox2p. However, deletion of the PNT1 orthologue from Kluyveromyces lactis, KlPNT1, caused a clear nonrespiratory phenotype, absence of cytochrome oxidase activity, and a defect in the assembly of KlCox2p that appears to be due to a block of C-tail export. Since PNT1 was previously described as a gene affecting resistance to the antibiotic pentamidine, our data support a mitochondrial target for this drug.

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“…These could include skin and blood cells, and possibly neuronal tissue, for the treatment of injury, for bone marrow transplants for leukaemia, and for degenerative diseases such as Parkinson's disease. One problem to be overcome is the existence of histocompatibility antigens encoded by mitochondrial DNA,5 but there may be various ways of altering their expression. Cloning techniques might also be useful in developing transgenic animals–for example, for human xenotransplantation.…”

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confidence: 99%

The promise of cloning for human medicine

Winston¹

1997

BMJ

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[34] MtDNA-encoded histocompatibility antigens

Cited by 22 publications

References 54 publications

Clinical features of MS associated with Leber hereditary optic neuropathy mtDNA mutations

Clinical features of MS associated with Leber hereditary optic neuropathy mtDNA mutations

Mutations Affecting a Yeast Mitochondrial Inner Membrane Protein, Pnt1p, Block Export of a Mitochondrially Synthesized Fusion Protein from the Matrix

The promise of cloning for human medicine

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