Mutational analysis in patients with neuromuscular disorders: Detection of mitochondrial deletion and double mutations in the MT-ATP6 gene

Felhi, Rahma; Mkaouar-Rebai, Emna; Sfaihi, Lamia; Alila-Fersi, Olfa; Tabebi, Mouna; Rhouma, Bochra Ben; Ammar, Marwa; Keskes, Leila; Hachicha, M.; Fakhfakh, Faiza

doi:10.1016/j.bbrc.2016.03.050

Cited by 11 publications

(6 citation statements)

References 23 publications

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“…The m.8932C > T ( a P136S) and m.8527A > G ( a M1V) were identified in children with neuromuscular disorders (Felhi et al, 2016 ). The first one was also identified in prostatic cancer cells (Petros et al, 2005 ).…”

Section: Pathogenic Mutations In Atp8 and Atp6mentioning

confidence: 99%

ATP Synthase Diseases of Mitochondrial Genetic Origin

et al. 2018

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Devastating human neuromuscular disorders have been associated to defects in the ATP synthase. This enzyme is found in the inner mitochondrial membrane and catalyzes the last step in oxidative phosphorylation, which provides aerobic eukaryotes with ATP. With the advent of structures of complete ATP synthases, and the availability of genetically approachable systems such as the yeast Saccharomyces cerevisiae, we can begin to understand these molecular machines and their associated defects at the molecular level. In this review, we describe what is known about the clinical syndromes induced by 58 different mutations found in the mitochondrial genes encoding membrane subunits 8 and a of ATP synthase, and evaluate their functional consequences with respect to recently described cryo-EM structures.

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Section: Pathogenic Mutations In Atp8 and Atp6mentioning

confidence: 99%

ATP Synthase Diseases of Mitochondrial Genetic Origin

et al. 2018

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“…Thus, these data suggests that the close proximity of the C8932T mutation may also promote tumor growth. Recent association of this mutation with neuromuscular disorders further supports this hypothesis along with predictions suggesting that this mutation would likely disrupt the protein structure [107]. This has important implications for patient populations as well, since the C8932T polymorphism was detected in two individuals during haplotype characterization [2].…”

Section: Mitochondrial Haplogroups and Cancermentioning

confidence: 87%

Roles of the mitochondrial genetics in cancer metastasis: not to be ignored any longer

Beadnell

Scheid

Vivian

et al. 2018

Cancer Metastasis Rev

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Mitochondrial DNA (mtDNA) encodes for only a fraction of the proteins that are encoded within the nucleus, and therefore has typically been regarded as a lesser player in cancer biology and metastasis. Accumulating evidence, however, supports an increased role for mtDNA impacting tumor progression and metastatic susceptibility. Unfortunately, due to this delay, there is a dearth of data defining the relative contributions of specific mtDNA polymorphisms (SNP), which leads to an inability to effectively use these polymorphisms to guide and enhance therapeutic strategies and diagnosis. In addition, evidence also suggests that differences in mtDNA impact not only the cancer cells, but also the cells within the surrounding tumor microenvironment, suggesting a broad encompassing role for mtDNA polymorphisms in regulating the disease progression. mtDNA may have profound implications in the regulation of cancer biology and metastasis. However, there are still great lengths to go to understand fully its contributions. Thus, herein we discuss the recent advances in our understanding of mtDNA in cancer and metastasis, providing a framework for future functional validation and discovery.

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“…Additional signs and symptoms were deafness, seizures, spastic paraplegia, neuropathy. Interestingly, Fehli et al reported a patient with psychomotor delay, global and axial hypotony and seizures and bilateral abnormalities of signal intensity in the bilateral lenticular nucleus, dentate nucleus and periventricular, carrying two homoplasmic variants: m.8392C>T (Pro136Ser) in MT-ATP6 gene and m.8527A>G at the junction MT-ATP6/MT-ATP8 [68].…”

Section: The Atp Synthase Deficiencymentioning

confidence: 99%

From the Structural and (Dys)function of ATP Synthase to Deficiency in Age-Related Diseases

Garone¹,

Pietra²,

Nesci³

2022

Preprint

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The ATP synthase is a mitochondrial complex embedded in the inner mitochondrial membrane. The enzyme is under the double genetic control of the mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). Fatal human diseases have been associated with defects in ATP synthase (Complex V) activity linked to mtDNA or nDNA pathogenetic variants in genes encoding structural subunits or assembly factors. Mitochondrial post-translational modifications of key amino acids, reduced/increased subunit expression, or protein to protein ATP synthase interaction, are also some of the mechanisms involved in the age-related disease pathway. All the major neurodegenerative diseases: Parkinson’s, Alzheimer’s and motor neuron diseases such as Amyotrophic Lateral Sclerosis highlight an impaired ATP generation in a mechanism involving the permeability transition pore that triggers a cellular homeostasis failure responsible for different forms of regulated cell death. In this review, we will explore ATP synthase assembly and function in physiological and pathological conditions by referring to the recent cryo-EM studies and by exploring human diseases models.

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Mutational analysis in patients with neuromuscular disorders: Detection of mitochondrial deletion and double mutations in the MT-ATP6 gene

Cited by 11 publications

References 23 publications

ATP Synthase Diseases of Mitochondrial Genetic Origin

ATP Synthase Diseases of Mitochondrial Genetic Origin

Roles of the mitochondrial genetics in cancer metastasis: not to be ignored any longer

From the Structural and (Dys)function of ATP Synthase to Deficiency in Age-Related Diseases

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