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Ndufaf5 deficiency in the Dictyostelium model: new roles in autophagy and development

AuthorsCarilla-Latorre, Sergio ; Annesley, Sarah J.; Muñoz-Braceras, Sandra ; Fisher, Paul R.; Escalante, Ricardo
Issue Date2013
PublisherAmerican Society for Cell Biology
CitationMolecular Biology of the Cell 24(10): 1519-1528 (2013)
AbstractNdufaf5 (also known as C20orf7) is a mitochondrial complex I (CI) assembly factor whose mutations lead to human mitochondrial disease. Little is known about the function of the protein and the cytopathological consequences of the mutations. Disruption of Dictyostelium Ndufaf5 leads to CI deficiency and defects in growth and development. The predicted sequence of Ndufaf5 contains a putative methyltransferase domain. Site-directed mutagenesis indicates that the methyltransferase motif is essential for its function. Pathological mutations were recreated in the Dictyostelium protein and expressed in the mutant background. These proteins were unable to complement the phenotypes, which further validates Dictyostelium as a model of the disease. Chronic activation of AMP-activated protein kinase (AMPK) has been proposed to play a role in Dictyostelium and human cytopathology in mitochondrial diseases. However, inhibition of the expression of AMPK gene in the Ndufaf5-null mutant does not rescue the phenotypes associated with the lack of Ndufaf5, suggesting that novel AMPK-independent pathways are responsible for Ndufaf5 cytopathology. Of interest, the Ndufaf5-deficient strain shows an increase in autophagy. This phenomenon was also observed in a Dictyostelium mutant lacking MidA (C2orf56/PRO1853/Ndufaf7), another CI assembly factor, suggesting that autophagy activation might be a common feature in mitochondrial CI dysfunction.
DescriptionThis article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
Publisher version (URL)http://dx.doi.org/10.1091/mbc.E12-11-0796
Identifiersdoi: 10.1091/mbc.E12-11-0796
issn: 1059-1524
e-issn: 1939-4586
Appears in Collections:(IIBM) Artículos
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