Maternally‐inherited Leigh syndrome‐related mutations bolster mitochondrial‐mediated apoptosis

@article{Carrozzo2004MaternallyinheritedLS,
  title={Maternally‐inherited Leigh syndrome‐related mutations bolster mitochondrial‐mediated apoptosis},
  author={Rosalba Carrozzo and Teresa Rizza and Annarita Stringaro and Roberta Pierini and Elisabetta Mormone and Filippo Maria Santorelli and Walter Malorni and Paola Matarrese},
  journal={Journal of Neurochemistry},
  year={2004},
  volume={90}
}
The key role of mitochondria in the apoptotic process is well understood, but not many data are available regarding the specific role of mitochondrial DNA mutations in determining cell fate. We investigated whether two mitochondrial DNA mutations (L217R and L156R) associated with maternally‐inherited Leigh syndrome may play a specific role in triggering the apoptotic cascade. Considering that different nuclear genetic factors may influence the expression of mtDNA mutations, we used a 143BTK… 
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References

SHOWING 1-10 OF 58 REFERENCES
Apoptosis in mitochondrial encephalomyopathies with mitochondrial DNA mutations: a potential pathogenic mechanism.
TLDR
This study suggests that apoptosis is not simply a means whereby cells with dysfunctional mitochondria are eliminated, but that it seems to play a role in the pathogenesis of mitochondrial disorders associated with mtDNA defects affecting mitochondrial protein synthesis.
Cells Bearing Mutations Causing Leber's Hereditary Optic Neuropathy Are Sensitized to Fas-induced Apoptosis*
TLDR
The data indicate that the most common and severe LHON pathogenic mutations 11778 and 3460 predispose cells to apoptosis, which may be relevant for the pathophysiology of cell death in LHON, and potential therapy.
Leber's Hereditary Optic Neuropathy (LHON) Pathogenic Mutations Induce Mitochondrial-dependent Apoptotic Death in Transmitochondrial Cells Incubated with Galactose Medium*
TLDR
Osteosarcoma-derived cytoplasmic hybrids (cybrid) cell lines harboring one of the three most frequent LHON pathogenic mutations, at positions 11778/ND4, 3460/ND1, and 14484/ND6, undergo cell death when galactose replaces glucose in the medium, contrary to control cybrids that maintain some growth capabilities.
The influence of nuclear background on the biochemical expression of 3460 Leber's hereditary optic neuropathy
TLDR
The results suggest that the nuclear environment can influence the expression of the biochemical defect in LHON patients with the A3460G mutation, and this defect was not apparent in all the clones studied.
Transglutaminase overexpression sensitizes neuronal cell lines to apoptosis by increasing mitochondrial membrane potential and cellular oxidative stress
TLDR
Results seem to suggest that, via hyperpolarization, tTG might act as a ‘sensitizer’ towards apoptotic stimuli specifically targeted to mitochondria, which could be of pathogenetic relevance for those diseases that are characterized by increased tTG and apoptotic rate together with impaired mitochondrial function, e.g. in some neurodegenerative disease.
Mitochondria and degenerative disorders.
In mammalian cells, mitochondria provide energy from aerobic metabolism. They play an important regulatory role in apoptosis, produce and detoxify free radicals, and serve as a cellular calcium…
Superoxide-induced massive apoptosis in cultured skin fibroblasts harboring the neurogenic ataxia retinitis pigmentosa (NARP) mutation in the ATPase-6 gene of the mitochondrial DNA.
TLDR
The oxidative stress resulting from the neurogenic ataxia retinitis pigmentosa (NARP) mutation in the mitochondrial ATPase 6 gene was investigated in cultured skin fibroblasts and established that the superoxide production associated with the ATPase deficiency triggered by the NARP mutation could be sufficient to override cell antioxidant defenses and to result in cell commitment to die.
Suppression of a mitochondrial tRNA gene mutation phenotype associated with changes in the nuclear background.
TLDR
The results suggest that modulation of the dosage or expression of unknown nuclear-coded factor(s) can compensate for a pathogenic mitochondrial tRNA gene mutation, suggesting new strategies for therapeutic intervention.
Protective effect of N-acetylcysteine in tumor necrosis factor-alpha-induced apoptosis in U937 cells: the role of mitochondria.
TLDR
Results show that TNF exposure is capable of altering the mitochondria and that NAC protection from CHX + TNF-induced apoptosis could be due to a direct effect of the drug on mitochondrial integrity and function.
The T9176G mtDNA mutation severely affects ATP production and results in Leigh syndrome
The authors identified a novel mtDNA mutation (T9176G) in the ATPase 6 gene in a family in which a 10-year-old girl had a severe neurodegenerative disorder, her elder sister had died of Leigh…
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