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Research Paper
Proteomic Analysis of Proteins Involved in Mitochondria-to-Nucleus Retrograde Response in Human Cancer Cells
Mariola Kulawiec, Hilal Arnouk, Mohamed Mokhtar Desouki, Latif Kazim, Ivan Still and Keshav K. Singh
volume 5 | issue 8
august 2006Pages: 967 - 968
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All tumors examined to date contain mutations in mitochondrial DNA (mtDNA). In addition, depletion of mtDNA is reported in a variety of tumors. Mitochondrial dysfunction resulting from changes in mtDNA invokes mitochondria-to-nucleus retrograde response in human cells. To identify proteins involved in retrograde response and their potential role in tumorigenesis, we carried out a comparative proteomic analysis using a cell line in which the mitochondrial genome was completely depleted (?0 cells lacking all mtDNA-encoded protein subunits), a cybrid cell line in which mtDNA was restored, and the parental cell line. Our comparative proteomic approach revealed marked changes in the cellular proteome and led us to identify quantitative changes in expression of several proteins. We found that subunits of complex I and complex III, molecular chaperones, and a protein involved in cell cycle control were down-regulated and Inosine 5’-monophosphate dehydrogenase type 2 (IMPDH2) involved in nucleotides biosynthesis was up-regulated in ?0 cells. Our findings demonstrate that the expression of proteins is restored to wild type level by transfer of wild type mitochondria to ?0 cells, suggesting that these proteins play key roles in retrograde response. To determine a potential role for identified retrograde responsive proteins in tumorigenesis, we analyzed the expression of UQCRC1 gene (encoding ubiquinol cytochrome-c reductase core protein I) in breast and ovarian tumors. We found that 1) UQCRC1 was highly expressed in breast (74%) and ovarian tumors (34%) and 2) the expression positively correlated with cytochrome c-oxidase (COXII) encoded by mtDNA. Our study opens an avenue for identification of retrograde proteins as potential tumor suppressors or oncogenes involved in carcinogenesis.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.