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

نویسندگان

  • Sergio Carilla-Latorre
  • M Esther Gallardo
  • Sarah J Annesley
  • Javier Calvo-Garrido
  • Osvaldo Graña
  • Sandra L Accari
  • Paige K Smith
  • Alfonso Valencia
  • Rafael Garesse
  • Paul R Fisher
  • Ricardo Escalante
چکیده

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.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

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

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 meth...

متن کامل

P-30: The Effect of The T26248G Polymorphism on Putative MethyltransferaseNsun7 Protein Function and Its Role in Male Infertility

Background: Male infertility has many causes, including genetic infertility. The NOP2/Sun domain family, member7 (Nsun7) gene, which encodes putative methyltransferase Nsun7, has a role in sperm motility. The aim of the present study was to investigate the effect of the T26248G polymorphism on Nsun7 protein function and its role in male infertility. Materials and Methods: Semen samples were col...

متن کامل

P-31: The Alteration of SpermatogenesisHas A Correlation with Sertoli Cell Mitochondrial Abnormal Morphology in Cytotoxicity of Testicular Tissue Mediatedwith Monosodium

Background: Male infertility has many causes, including genetic infertility. The NOP2/Sun domain family, member7 (Nsun7) gene, which encodes putative methyltransferase Nsun7, has a role in sperm motility. The aim of the present study was to investigate the effect of the T26248G polymorphism on Nsun7 protein function and its role in male infertility. Materials and Methods: Semen samples were col...

متن کامل

Function of mitochondrial complex-I and -IV in normal human and Parkinson's disease cybrids

Mitochondrial dysfunction has been implicated in the dopaminergic neurodegeneration, which characterizes Parkinson’s disease (PD). The activities of mitochondrial complexes I and IV were found to be reduced in the brains of PD patients (n = 4) as compared to age-matched controls (n = 4). This is tested in SH-SY5Y cell lines, transformed Rho0 cells, and in normal and PD cybrid cell lines. Cybrid...

متن کامل

Function of mitochondrial complex-I and -IV in normal human and Parkinson's disease cybrids

Mitochondrial dysfunction has been implicated in the dopaminergic neurodegeneration, which characterizes Parkinson’s disease (PD). The activities of mitochondrial complexes I and IV were found to be reduced in the brains of PD patients (n = 4) as compared to age-matched controls (n = 4). This is tested in SH-SY5Y cell lines, transformed Rho0 cells, and in normal and PD cybrid cell lines. Cybrid...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Journal of cell science

دوره 123 Pt 10  شماره 

صفحات  -

تاریخ انتشار 2010