Neonatal mitochondrial encephaloneuromyopathy due to a defect of mitochondrial protein synthesis

Ferreiro-Barros, Claudia Cristina; Tengan, Célia Harumi; Barros, Mário H.; Palenzuela, Lluís; Kanki, Chisaka; Quinzii, Catarina M.; Lou, Johanna; Gharaby, Nader El; Shokr, Aly; Vivo, Darryl C. De; DiMauro, Salvatore; Hirano, Michio

doi:10.1016/j.jns.2008.08.028

Cited by 12 publications

(15 citation statements)

References 25 publications

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“…One possibility is that Msc6p improves the stringency with which mIF-2 positions the fMet-tRNA fMet on the mRNA and the ribosomal small subunit. Despite the well-known consequences of mitochondrial translation impairments in human diseases [8,39,40], a recent study also unveiled that mitochondrial translation accuracy directly affects the proteostatic capacity of the cytoplasm as well as coordinates nuclear stress signaling and cellular life span [22]. Here we showed that msc6 and ifm1 mutants present low viability in two different longevity/survival assays in agreement with some recent data [22] but distinct from others mitochondrial translational factors mutants [41,42].…”

Section: Discussionsupporting

confidence: 92%

Msc6p is required for mitochondrial translation initiation in the absence of formylated Met‐tRNA^fMet

et al. 2019

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Mitochondrial translation normally requires formylation of the initiator tRNA‐met, a reaction catalyzed by the enzyme formyltransferase, Fmt1p and MTFMT in Saccharomyces cerevisiae and human mitochondria, respectively. Yeast fmt1 mutants devoid of Fmt1p, however, can synthesize all mitochondrial gene products by initiating translation with a non‐formylated methionyl‐tRNA. Yeast synthetic respiratory‐deficient fmt1 mutants have uncovered several factors suggested to play a role in translation initiation with non‐formylated methionyl‐tRNA. Here, we present evidence that Msc6p, a member of the pentatricopeptide repeat (PPR) motif family, is another essential factor for mitochondrial translation in fmt1 mutants. The PPR motif is characteristic of RNA‐binding proteins found in chloroplasts and plant and fungal mitochondria, and is generally involved in RNA stability and transport. Moreover, in the present study, we show that the respiratory deficiency of fmt1msc6 double mutants can be rescued by overexpression of the yeast mitochondrial initiation factor mIF‐2, encoded by IFM1. The role of Msc6p in translational initiation is further supported by pull‐down assays showing that it transiently interacts with mIF‐2. Altogether, our data indicate that Msc6p is an important factor in mitochondrial translation with an auxiliary function related to the mIF‐2‐dependent formation of the initiation complex.

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Section: Discussionsupporting

confidence: 92%

Msc6p is required for mitochondrial translation initiation in the absence of formylated Met‐tRNA^fMet

et al. 2019

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“…These disorders are generally multisystemic [6, 8] and may be present at any age [7], and the global prevalence, probably underestimated, is 1/8500 [7]. The organs with highest energy demand, such as, heart, brain, skeletal muscle tissue, and liver, are preferentially involved [6, 8–11].…”

Section: Introductionmentioning

confidence: 99%

“…Mitochondrial disorders are a heterogeneous group of diseases characterized by defects of mitochondrial structure and oxidative phosphorylation [ 6 – 8 ]. These disorders are generally multisystemic [ 6 , 8 ] and may be present at any age [ 7 ], and the global prevalence, probably underestimated, is 1/8500 [ 7 ]. The organs with highest energy demand, such as, heart, brain, skeletal muscle tissue, and liver, are preferentially involved [ 6 , 8 – 11 ].…”

Section: Introductionmentioning

confidence: 99%

Neurofibromatosis Type 1: A Novel NF1 Mutation Associated with Mitochondrial Complex I Deficiency

Domingues

Isidoro

Rocha

et al. 2014

Case Reports in Genetics

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Background. Neurofibromatosis type 1 is a multisystemic, progressive disease, with an estimated incidence of 1/3500-2500. Mitochondrial diseases are generally multisystemic and may be present at any age, and the global prevalence is 1/8500. The diagnosis of these disorders is complex because of its clinical and genetic heterogeneity. Case Report. We present a rare case of the association of these two different genetic diseases, in which a heterozygous missense mutation in the NF1 gene was identified which had not yet been described (p.M1149 V). Additionally, the patient is suspected of carrying an unspecified mutation causing respiratory chain complex I deficiency. Clinical presentation included hypotonia, global development delay, reduced growth rate, progressive microcephaly, and numerous café-au-lait spots. Discussion. To the best of our knowledge this is the first report of complex I deficiency in a patient with neurofibromatosis type 1. It is very important to maintain a high index of suspicion for the diagnosis of mitochondrial disorders. In this patient, both the laboratory screening and muscle histology were normal and only the biochemical study of muscle allowed us to confirm the diagnosis.

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“…Recently it was shown that patients with mutations in the RMND1 gene present impaired mitochondrial translation [68][69][70]. Defective RMND1 lead to lower steady state level of ribosome subunits MRPL13, MRPL32, MRPS2, as well as lower content of 16S rRNA indicating a role for RMND1 in the assembly or maintenance of mitochondrial ribosome [68,70].…”

Section: Ribosome Biogenesis and Proteinsmentioning

confidence: 99%

Mitochondrial Translation in Health and Disease

Ferreiro-Barros¹,

Barros²

2013

OJEMD

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Mitochondrial disorders have become the most common cause of inborn errors of metabolism. Impairments in mitochondrial protein synthesis are one of the causes of these diseases, which are clinically and genetically heterogeneous. The mitochondrial translation machinery decodes 13 polypeptides essential for the oxidative phosphorylation process. Mitochondria protein synthesis depends on the integrity of mitochondrial rRNAs and tRNAs genes, and at least one hundred of nuclear encoded products. Diseases caused by mutations in mitochondrial genes as well as in ribosomal proteins, translational factors, RNA modifying enzymes, and all other constituents of the translational machinery have been described in patients with combine respiratory chain deficiency, and are the object of this review.

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Neonatal mitochondrial encephaloneuromyopathy due to a defect of mitochondrial protein synthesis

Cited by 12 publications

References 25 publications

Msc6p is required for mitochondrial translation initiation in the absence of formylated Met‐tRNA^fMet

Msc6p is required for mitochondrial translation initiation in the absence of formylated Met‐tRNA^fMet

Neurofibromatosis Type 1: A Novel NF1 Mutation Associated with Mitochondrial Complex I Deficiency

Mitochondrial Translation in Health and Disease

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Neonatal mitochondrial encephaloneuromyopathy due to a defect of mitochondrial protein synthesis

Cited by 12 publications

References 25 publications

Msc6p is required for mitochondrial translation initiation in the absence of formylated Met‐tRNAfMet

Msc6p is required for mitochondrial translation initiation in the absence of formylated Met‐tRNAfMet

Neurofibromatosis Type 1: A Novel NF1 Mutation Associated with Mitochondrial Complex I Deficiency

Mitochondrial Translation in Health and Disease

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Product

Resources

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Msc6p is required for mitochondrial translation initiation in the absence of formylated Met‐tRNA^fMet

Msc6p is required for mitochondrial translation initiation in the absence of formylated Met‐tRNA^fMet