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  current news   Press   selected story    
     
  5th May  
 

GRIM-19 Is Essential for Maintenance of Mitochondrial Membrane Potential

 
 




Authors
Hao Lu and Xinmin Cao

Abstract
GRIM-19 was found to copurify with complex I of mitochondrial respiratory chain and subsequently was demonstrated to be involved in complex I assembly and activity. To further understand its function in complex I, we dissected its functional domains by generating a number of deletion, truncation, and point mutants. The mitochondrial localization sequences were located at the N-terminus. Strikingly, deletion of residues 7080, 90100, or the whole C-terminal region (70144) led to a loss of mitochondrial transmembrane potential (m). However, similar deletions of another two complex I subunits, NDUFA9 and NDUFS3, did not show such effect. We also found that deletion of the last 10 residues affected GRIM-19's ability to be assembled to complex I. We constructed a dominant-negative mutant containing the N-terminal 60 and the last C-terminal 10 residues, which could be assembled into complex I, but failed to maintain normal m. Cells overexpressing this mutant did not spontaneously undergo cell death, but were sensitized to apoptosis induced by cell death agents. Our results demonstrate that GRIM-19 is required for electron transfer activity of complex I, and disruption of m by GRIM-19 mutants enhances the cells' sensitivity to apoptotic stimuli.

 
 


 
 

Dominant negative-GRIM-19 strongly reduces the mitochondrial membrane potential.
(A) Schematic diagram of dominate-negative (DN)-GRIM-19. (B) Wild-type and DN-GRIM-19 were transfected into MCF-7 cells.GRIM-19 proteins were detected by anti-HA primary antibody and FITC-conjugated secondary antibody (green). Mitochondrial membrane potential was detected with Mito-Tracker CMXRos (red). Nuclei were stained with TOPRO-3 (blue). The merged images are shown. (C).Functional domains of GRIM-19 identified in this paper.n.

Mol. Biol. Cell 2008 Vol 19: 1893-1902.
First Published on February 20 2008; 10.1091/mbc.E07-07-0683

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