MidA is a putative methyltransferase that is required for mitochondrial complex I function

作者：Carilla Latorre Sergio; Esther Gallardo M; Annesley Sarah J; Calvo Garrido Javier; Grana Osvaldo; Accari Sandra L; Smith Paige K; Valencia Alfonso; Garesse Rafael; Fisher Paul R; Escalante Ricardo^*

来源：Journal of Cell Science, 2010, 123(10): 1674-1683.

DOI：10.1242/jcs.066076

• Dictyostelium
• Complex I
• MidA
• PRO1853
• C2orf56
• LOC55471
• DUF185

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.

• 出版日期2010-5-15