MidA is a putative methyltransferase that is required for mitochondrial complex I function Academic Article uri icon

abstract

  • 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.

authors

  • Carilla-Latorre, S
  • Gallardo, ME
  • Annesley, SJ
  • Calvo-Garrido, J
  • Grana, O
  • Accari, SL
  • Smith, PK
  • Valencia, A
  • Garesse, R
  • Fisher, PR
  • Escalante, R

publication date

  • May 15, 2010