TY - JOUR
T1 - Methylation-controlled J-protein MCJ acts in the import of proteins into human mitochondria
AU - Schusdziarra, Christina
AU - Blamowska, Marta
AU - Azem, Abdussalam
AU - Hell, Kai
N1 - Funding Information: This work was supported by the Deutsche Forschungsge-meinschaft (SFB 594, B13 to K.H.), by the German-Israeli Foundation for Scientific Research and Development (GIF-1012/08 to A.A.), the Israel Science Foundation (452/ 09 to A.A.) and by a predoctoral fellowship from the Elite Netzwerk Bayern to C.S.
PY - 2013/4
Y1 - 2013/4
N2 - Loss of expression of the methylation-controlled J gene, MCJ (DNAJC15), is observed in cases of several tumors and plays a crucial role in the chemoresistance of ovarian cancer cells. Aside from the pathophysiological effects, almost nothing is known about the cellular function of MCJ. Here, we provide the first evidence that MCJ acts in the biogenesis of mitochondria. Our results demonstrate that MCJ is located in mitochondria. It is anchored in the mitochondrial inner membrane with the C-terminal J domain facing the matrix space. We show that MCJ forms a stable subcomplex with a component of the mitochondrial import motor, MAGMAS, a protein overexpressed in cells treated with granulocyte-macrophage colony-stimulating factor and in prostate carcinomas. In addition, MCJ and MAGMAS interact with the core components of the TIM23 pre-protein translocase. We demonstrate that the recombinant soluble MCJ domain stimulates the ATPase activity of the human mtHsp70 chaperone, mortalin, the central component of the import motor of the TIM23 translocase. This stimulation is counteracted by MAGMAS. Moreover, pre-protein import into mitochondria is impaired in the absence of MCJ. Interestingly, MCJ is able to take over the function of Tim14, the essential J co-chaperone of the mitochondrial protein import motor in yeast. In summary, our results show that MCJ functions as J co-chaperone of the human TIM23 pre-protein translocase, suggesting a link between mitochondrial pre-protein import and tumorigenesis.
AB - Loss of expression of the methylation-controlled J gene, MCJ (DNAJC15), is observed in cases of several tumors and plays a crucial role in the chemoresistance of ovarian cancer cells. Aside from the pathophysiological effects, almost nothing is known about the cellular function of MCJ. Here, we provide the first evidence that MCJ acts in the biogenesis of mitochondria. Our results demonstrate that MCJ is located in mitochondria. It is anchored in the mitochondrial inner membrane with the C-terminal J domain facing the matrix space. We show that MCJ forms a stable subcomplex with a component of the mitochondrial import motor, MAGMAS, a protein overexpressed in cells treated with granulocyte-macrophage colony-stimulating factor and in prostate carcinomas. In addition, MCJ and MAGMAS interact with the core components of the TIM23 pre-protein translocase. We demonstrate that the recombinant soluble MCJ domain stimulates the ATPase activity of the human mtHsp70 chaperone, mortalin, the central component of the import motor of the TIM23 translocase. This stimulation is counteracted by MAGMAS. Moreover, pre-protein import into mitochondria is impaired in the absence of MCJ. Interestingly, MCJ is able to take over the function of Tim14, the essential J co-chaperone of the mitochondrial protein import motor in yeast. In summary, our results show that MCJ functions as J co-chaperone of the human TIM23 pre-protein translocase, suggesting a link between mitochondrial pre-protein import and tumorigenesis.
UR - http://www.scopus.com/inward/record.url?scp=84875252342&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/hmg/dds541
DO - https://doi.org/10.1093/hmg/dds541
M3 - مقالة
SN - 0964-6906
VL - 22
SP - 1348
EP - 1357
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 7
M1 - dds541
ER -