| Author | Santos, Manuella Maria Silva | |
| Author | Elsztein, Carolina | |
| Author | Souza, Rafael Barros de | |
| Author | Paiva, Sérgio de Sá Leitão | |
| Author | Silva, Jaqueline Azevêdo | |
| Author | Crovella, Sergio | |
| Author | Morais Junior, Marcos Antonio de | |
| Access date | 2019-05-16T14:15:17Z | |
| Available date | 2019-05-16T14:15:17Z | |
| Document date | 2018 | |
| Citation | SANTOS, Manuella Maria Silva et al. Respiratory Deficiency in Yeast Mevalonate Kinase Deficient May Explain MKD-Associate Metabolic Disorder in Humans. Current Genetics, v. 64, n. 4, p. 871-881, Aug. 2018. | pt_BR |
| ISSN | 1432-0983 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/33113 | |
| Language | eng | pt_BR |
| Rights | restricted access | pt_BR |
| Title | Respiratory deficiency in yeast mevalonate kinase deficient may explain MKD-associate metabolic disorder in humans | pt_BR |
| Type | Article | |
| DOI | 10.1007/s00294-018-0803-2 | |
| Abstract | Mevalonate kinase deficiency (MKD) an orphan drug rare disease affecting humans with different clinical presentations, is still lacking information about its pathogenesis; no animal or cell model mimicking the genetic defect, mutations at MVK gene, and its consequences on the mevalonate pathway is available. Trying to clarify the effects of MVK gene impairment on the mevalonate pathway we used a yeast model, the erg12-d mutant strain Saccharomyces cerevisiae (orthologous of MKV) retaining only 10% of mevalonate kinase (MK) activity, to describe the effects of reduced MK activity on the mevalonate pathway. Since shortage of isoprenoids has been described in MKD, we checked this observation using a physiologic approach: while normally growing on glucose, erg12-d showed growth deficiency in glycerol, a respirable carbon source, that was not rescued by supplementation with non-sterol isoprenoids, such as farnesol, geraniol nor geranylgeraniol, produced by the mevalonate pathway. Erg12-d whole genome expression analysis revealed specific downregulation of RSF2 gene encoding general transcription factor for respiratory genes, explaining the absence of growth on glycerol. Moreover, we observed the upregulation of genes involved in sulphur amino acids biosynthesis that coincided with the increasing in the amount of proteins containing sulfhydryl groups; upregulation of ubiquinone biosynthesis genes was also detected. Our findings demonstrated that the shortage of isoprenoids is not the main mechanism involved in the respiratory deficit and mitochondrial malfunctioning of MK-defective cells, while the scarcity of ubiquinone plays an important role, as already observed in MKD patients. | pt_BR |
| Affilliation | Federal University of Pernambuco. Interdepartmental Research Group in Metabolic Engineering. Recife, PE, Brazil / Federal University of Pernambuco. Department of Genetics. Recife, PE, Brazil. | pt_BR |
| Affilliation | Federal University of Pernambuco. Interdepartmental Research Group in Metabolic Engineering. Recife, PE, Brazil / Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Virologia. Recife, PE, Brasil. | pt_BR |
| Affilliation | Federal University of Pernambuco. Interdepartmental Research Group in Metabolic Engineering. Recife, PE, Brazil / University of Pernambuco. Institute for Biologial Sciences. Recife, PE, Brazil. | pt_BR |
| Affilliation | Federal Rural University Pernambuco. Laboratory of Bioinformatics and Evolutionary Biology. Recife, PE, Brazil. | pt_BR |
| Affilliation | Federal University of Pernambuco. Department of Genetics. Recife, PE, Brazil / Federal University of Pernambuco. Laboratory of Immunopathology Keizo Asami. Recife, PE, Brazil. | pt_BR |
| Affilliation | Federal University of Pernambuco. Department of Genetics. Recife, PE, Brazil / Federal University of Pernambuco. Laboratory of Immunopathology Keizo Asami. Recife, PE, Brazil. | pt_BR |
| Affilliation | Federal University of Pernambuco. Interdepartmental Research Group in Metabolic Engineering. Recife, PE, Brazil / Federal University of Pernambuco. Department of Genetics. Recife, PE, Brazil. | pt_BR |
| Subject | Isoprenoids | pt_BR |
| Subject | Gene expression | pt_BR |
| Subject | Microarray | pt_BR |
| Subject | Respiratory metabolism | pt_BR |
| Subject | Yeast | pt_BR |
| DeCS | Regulação da Expressão Gênica Fúngica | pt_BR |
| DeCS | Genoma Fúngico | pt_BR |
| DeCS | Humanos | pt_BR |
| DeCS | Deficiência de Mevalonato Cinase / genética | pt_BR |
| DeCS | Deficiência de Mevalonato Cinase / metabolismo | pt_BR |
| DeCS | Deficiência de Mevalonato Cinase / patologia | pt_BR |
| DeCS | Mutação | pt_BR |
| DeCS | Fosfotransferases (Aceitador do Grupo do Álcool) / deficiência | pt_BR |
| DeCS | Fosfotransferases (Aceitador do Grupo do Álcool) / genética | pt_BR |
| DeCS | Respiração / genética | pt_BR |
| DeCS | Saccharomyces cerevisiae / enzimologia | pt_BR |
| DeCS | Saccharomyces cerevisiae / genética | pt_BR |
| DeCS | Proteínas de Saccharomyces cerevisiae / genética | pt_BR |
| DeCS | Terpenos / metabolismo | pt_BR |
| DeCS | Fatores de Transcrição / genética | pt_BR |
| DeCS | Ubiquinona / genética | pt_BR |
| DeCS | Ubiquinona / metabolismo | pt_BR |
| Embargo date | 2050-01-01 | |
