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Charcot-Marie-Tooth-related gene GDAP1 complements cell cycle delay at G2/M phase in Saccharomyces cerevisiae fis1 gene-defective cells

AuthorsEstela, Anna ; Pla-Martín, David ; Sánchez-Piris, Maribel; Sesaki, Hiromi; Palau Martínez, Francesc
Issue Date2-Sep-2011
PublisherAmerican Society for Biochemistry and Molecular Biology
CitationJournal of Biological Chemistry 286(42): 36777-86 (2011 Oct 21)
AbstractMutations in the GDAP1 gene are responsible of the Charcot-Marie-Tooth CMT4A, ARCMT2K, and CMT2K variants. GDAP1 is a mitochondrial outer membrane protein that has been related to the fission pathway of the mitochondrial network dynamics. As mitochondrial dynamics is a conserved process, we reasoned that expressing GDAP1 in Saccharomyces cerevisiae strains defective for genes involved in mitochondrial fission or fusion could increase our knowledge of GDAP1 function. We discovered a consistent relation between Fis1p and the cell cycle because fis1Δ cells showed G(2)/M delay during cell cycle progression. The fis1Δ phenotype, which includes cell cycle delay, was fully rescued by GDAP1. By contrast, clinical missense mutations rescued the fis1Δ phenotype except for the cell cycle delay. In addition, both Fis1p and human GDAP1 interacted with β-tubulins Tub2p and TUBB, respectively. A defect in the fis1 gene may induce abnormal location of mitochondria during budding mitosis, causing the cell cycle delay at G(2)/M due to its anomalous interaction with microtubules from the mitotic spindle. In the case of neurons harboring defects in GDAP1, the interaction between mitochondria and the microtubule cytoskeleton would be altered, which might affect mitochondrial axonal transport and movement within the cell and may explain the pathophysiology of the GDAP1-related Charcot-Marie-Tooth disease.
Description10 páginas, 6 figuras, 2 tablas. PMID:21890626[PubMed] PMCID:PMC3196079[Available on 2012/10/21]
Publisher version (URL)http://dx.doi.org/10.1074/jbc.M111.260042
Appears in Collections:(IBV) Artículos
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Estela_et_al-manuscript file_JBC-2011-260042.pdfArtículo principal269,82 kBAdobe PDFThumbnail
Figures-Estela et al.pdfFiguras3,14 MBAdobe PDFThumbnail
Supplemental data-JBC-2011-260042.pdfInformación suplementaria108,17 kBAdobe PDFThumbnail
Supplemental figures-Estela et al.pdfInformación suplementaria de figuras1,02 MBAdobe PDFThumbnail
SM Tables-JBC-2011-260042.pdfTablas203,2 kBAdobe PDFThumbnail
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