Journal
JOURNAL OF CELL SCIENCE
Volume 123, Issue 10, Pages 1674-1683Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.066076
Keywords
Dictyostelium; Complex I; MidA; PRO1853; C2orf56; LOC55471; DUF185
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Funding
- Spanish Ministerio de Ciencia e Innovacion [BMC2006-00394, BMC2009-09050]
- Thyne Reid Memorial Trusts
- Australian Research Council
- Spanish National Bioinformatics Institute
- Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain [PI070167]
- Comunidad de Madrid [GEN-0269/2006]
- Consejer a de Educacion de la Comunidad de Madrid y del Fondo Social Europeo (FSE)
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Dictyostelium and human MidA are homologous proteins that belong to a family of proteins of unknown function called DUF185. Using yeast two-hybrid screening and pull-down experiments, we showed that both proteins interact with the mitochondrial complex I subunit NDUFS2. Consistent with this, Dictyostelium cells lacking MidA showed a specific defect in complex I activity, and knockdown of human MidA in HEK293T cells resulted in reduced levels of assembled complex I. These results indicate a role for MidA in complex I assembly or stability. A structural bioinformatics analysis suggested the presence of a methyltransferase domain; this was further supported by site-directed mutagenesis of specific residues from the putative catalytic site. Interestingly, this complex I deficiency in a Dictyostelium midA-mutant causes a complex phenotypic outcome, which includes phototaxis and thermotaxis defects. We found that these aspects of the phenotype are mediated by a chronic activation of AMPK, revealing a possible role of AMPK signaling in complex I cytopathology.
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