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Research on plants for the understanding of diseases of nuclear and mitochondrial origin.

Spampinato CP, Gomez-Casati DF - J. Biomed. Biotechnol. (2012)

Bottom Line: Different model organisms, such as Escherichia coli, Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, mouse, cultured human cell lines, among others, were used to study the mechanisms of several human diseases.Since human genes and proteins have been structurally and functionally conserved in plant organisms, the use of plants, especially Arabidopsis thaliana, as a model system to relate molecular defects to clinical disorders has recently increased.Here, we briefly review our current knowledge of human diseases of nuclear and mitochondrial origin and summarize the experimental findings of plant homologs implicated in each process.

View Article: PubMed Central - PubMed

Affiliation: Centro de Estudios Fotosintéticos y Bioquímicos-CEFOBI-CONICET, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina. spampinato@cefobi-conicet.gov.ar

ABSTRACT
Different model organisms, such as Escherichia coli, Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, mouse, cultured human cell lines, among others, were used to study the mechanisms of several human diseases. Since human genes and proteins have been structurally and functionally conserved in plant organisms, the use of plants, especially Arabidopsis thaliana, as a model system to relate molecular defects to clinical disorders has recently increased. Here, we briefly review our current knowledge of human diseases of nuclear and mitochondrial origin and summarize the experimental findings of plant homologs implicated in each process.

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Related in: MedlinePlus

Sequence alignment of NDUFS4 homologues from different organisms showing the high conservation in the flanking region of D119. The amino acid sequence of Homo sapiens (accession no. NP_002486.1), Mus musculus (accession no. NP_035017.2), Bos taurus (accession no. DAA17925.1), Drosophila melanogaster (accession no. NP_573385), Arabidopsis thaliana (accession no. Q9FJW4), Populus trichocarpa (accession no. XP_002310893), Hordeum vulgare (accession no. BAK01929), Zea mays (accession no. NP_001132398), Oryza sativa (accession no. NP_001060126) and Glycine max (accession no. NP_001235335) are shown. Alignment was performed by using the CLUSTALW2 method (Protein Weight Matrix Blosum, clustering NJ) (http://www.ebi.ac.uk/Tools/msa/clustalw2/). The conserved Asp residue is shown in grey.
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fig2: Sequence alignment of NDUFS4 homologues from different organisms showing the high conservation in the flanking region of D119. The amino acid sequence of Homo sapiens (accession no. NP_002486.1), Mus musculus (accession no. NP_035017.2), Bos taurus (accession no. DAA17925.1), Drosophila melanogaster (accession no. NP_573385), Arabidopsis thaliana (accession no. Q9FJW4), Populus trichocarpa (accession no. XP_002310893), Hordeum vulgare (accession no. BAK01929), Zea mays (accession no. NP_001132398), Oryza sativa (accession no. NP_001060126) and Glycine max (accession no. NP_001235335) are shown. Alignment was performed by using the CLUSTALW2 method (Protein Weight Matrix Blosum, clustering NJ) (http://www.ebi.ac.uk/Tools/msa/clustalw2/). The conserved Asp residue is shown in grey.

Mentions: The first mutation found in NDUFS4 was a 5-bp duplication in the ORF of the gene that impairs the phosphorylation of the protein leading to an inactivation of the complex [162, 163]. Other mutations in patients with Leigh syndrome were found in NDUFS4 such as a homozygous G-A transition at nucleotide +44 of the coding sequence [164]. The G44A mutation results in the change of a TGG codon, which encodes for a tryptophan residue, to a TAA stop codon, which causes the premature termination of the protein, thus obtaining a truncated form of NDUFS4. A third mutation in NDUSF4 was reported, a single-base deletion at position 289/290 [165]. Recently, two novel mutations in NDUFS4 causing Leigh syndrome has been reported [166]. One of these mutations, D119H, is in a conserved region of the protein. Interestingly, the D119 is highly conserved within human, mammals, nematodes, and plant species (Figure 2). All the mentioned mutations were found to be associated with a defect of the assembly of a functional complex in the inner mitochondrial membrane. These data suggest that NDUFS4 has an essential role in the structure and function of CI.


Research on plants for the understanding of diseases of nuclear and mitochondrial origin.

Spampinato CP, Gomez-Casati DF - J. Biomed. Biotechnol. (2012)

Sequence alignment of NDUFS4 homologues from different organisms showing the high conservation in the flanking region of D119. The amino acid sequence of Homo sapiens (accession no. NP_002486.1), Mus musculus (accession no. NP_035017.2), Bos taurus (accession no. DAA17925.1), Drosophila melanogaster (accession no. NP_573385), Arabidopsis thaliana (accession no. Q9FJW4), Populus trichocarpa (accession no. XP_002310893), Hordeum vulgare (accession no. BAK01929), Zea mays (accession no. NP_001132398), Oryza sativa (accession no. NP_001060126) and Glycine max (accession no. NP_001235335) are shown. Alignment was performed by using the CLUSTALW2 method (Protein Weight Matrix Blosum, clustering NJ) (http://www.ebi.ac.uk/Tools/msa/clustalw2/). The conserved Asp residue is shown in grey.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368588&req=5

fig2: Sequence alignment of NDUFS4 homologues from different organisms showing the high conservation in the flanking region of D119. The amino acid sequence of Homo sapiens (accession no. NP_002486.1), Mus musculus (accession no. NP_035017.2), Bos taurus (accession no. DAA17925.1), Drosophila melanogaster (accession no. NP_573385), Arabidopsis thaliana (accession no. Q9FJW4), Populus trichocarpa (accession no. XP_002310893), Hordeum vulgare (accession no. BAK01929), Zea mays (accession no. NP_001132398), Oryza sativa (accession no. NP_001060126) and Glycine max (accession no. NP_001235335) are shown. Alignment was performed by using the CLUSTALW2 method (Protein Weight Matrix Blosum, clustering NJ) (http://www.ebi.ac.uk/Tools/msa/clustalw2/). The conserved Asp residue is shown in grey.
Mentions: The first mutation found in NDUFS4 was a 5-bp duplication in the ORF of the gene that impairs the phosphorylation of the protein leading to an inactivation of the complex [162, 163]. Other mutations in patients with Leigh syndrome were found in NDUFS4 such as a homozygous G-A transition at nucleotide +44 of the coding sequence [164]. The G44A mutation results in the change of a TGG codon, which encodes for a tryptophan residue, to a TAA stop codon, which causes the premature termination of the protein, thus obtaining a truncated form of NDUFS4. A third mutation in NDUSF4 was reported, a single-base deletion at position 289/290 [165]. Recently, two novel mutations in NDUFS4 causing Leigh syndrome has been reported [166]. One of these mutations, D119H, is in a conserved region of the protein. Interestingly, the D119 is highly conserved within human, mammals, nematodes, and plant species (Figure 2). All the mentioned mutations were found to be associated with a defect of the assembly of a functional complex in the inner mitochondrial membrane. These data suggest that NDUFS4 has an essential role in the structure and function of CI.

Bottom Line: Different model organisms, such as Escherichia coli, Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, mouse, cultured human cell lines, among others, were used to study the mechanisms of several human diseases.Since human genes and proteins have been structurally and functionally conserved in plant organisms, the use of plants, especially Arabidopsis thaliana, as a model system to relate molecular defects to clinical disorders has recently increased.Here, we briefly review our current knowledge of human diseases of nuclear and mitochondrial origin and summarize the experimental findings of plant homologs implicated in each process.

View Article: PubMed Central - PubMed

Affiliation: Centro de Estudios Fotosintéticos y Bioquímicos-CEFOBI-CONICET, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina. spampinato@cefobi-conicet.gov.ar

ABSTRACT
Different model organisms, such as Escherichia coli, Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, mouse, cultured human cell lines, among others, were used to study the mechanisms of several human diseases. Since human genes and proteins have been structurally and functionally conserved in plant organisms, the use of plants, especially Arabidopsis thaliana, as a model system to relate molecular defects to clinical disorders has recently increased. Here, we briefly review our current knowledge of human diseases of nuclear and mitochondrial origin and summarize the experimental findings of plant homologs implicated in each process.

Show MeSH
Related in: MedlinePlus