dictyNews Volume 39 Number 09

Published in

· 1 year ago

dictyNews 
Electronic Edition 
Volume 39, number 9 
March 29, 2013 

Please submit abstracts of your papers as soon as they have been 
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========= 
Abstracts 
========= 

 

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

Sergio Carilla-Latorre, Sarah J. Annesley, Sandra  
Muoz-Braceras, Paul R. Fisher, and Ricardo Escalante 

Molecular Biology of the Cell, in press 

Ndufaf5 (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 of Ndufaf5 cytopathology.   
Interestingly, 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. 

  
Submitted by Ricardo Escalante [rescalante@iib.uam.es] 
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[End dictyNews, volume 39, number 9]