CHOP (C/EBP homologous protein) and ASNS (asparagine synthetase) induction in cybrid cells harboring MELAS and NARP mitochondrial DNA mutations. Export

@article{citeulike:4732051, abstract = {Mitochondrial dysfunction caused by mutations in mitochondrial DNA (mtDNA) is related to a variety of diseases including MELAS and NARP syndromes. However, little is known about the intracellular responses induced by mtDNA mutations. In order to identify genes whose expression is altered as a result of the presence of mtDNA mutations, DNA microarray analysis was performed using human 143B osteosarcoma cells harboring 3243A>G [tRNA-Leu (UUR)] and 8993T>G [ATPase6 Leu156Arg] mtDNA mutations associated with MELAS and NARP syndromes (2SD and NARP3-1 cybrid cells), respectively. We found that mRNA and protein levels of ATF4, CHOP and ASNS were upregulated in 2SD and NARP3-1 cells as compared with parental cells. Reporter assays demonstrated that transcription of CHOP and ASNS genes was upregulated through the AARE (amino acid regulatory element) and NSRE-1 (nutrient-sensing response element-1) enhancer elements to which ATF4 binds, respectively. Furthermore, knockdown of ATF4 by RNA interference reduced CHOP and ASNS transcription in 2SD and NARP3-1 cells. These results suggest that the presence of mtDNA mutations elicits upregulation of CHOP and ASNS genes through the elevation of ATF4 expression and its binding to the AARE and NSRE-1, respectively.}, author = {Fujita, Y. and Ito, M. and Nozawa, Y. and Yoneda, M. and Oshida, Y. and Tanaka, M.}, citeulike-article-id = {4732051}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.mito.2006.11.003}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S1567724906002200}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/17276738}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=17276738}, doi = {10.1016/j.mito.2006.11.003}, issn = {1567-7249}, journal = {Mitochondrion}, keywords = {analysis, array, human, mitochondria, narp, projnarp}, number = {1-2}, pages = {80--88}, posted-at = {2009-06-03 12:52:17}, priority = {2}, title = {CHOP (C/EBP homologous protein) and ASNS (asparagine synthetase) induction in cybrid cells harboring MELAS and NARP mitochondrial DNA mutations.}, url = {http://dx.doi.org/10.1016/j.mito.2006.11.003}, volume = {7}, year = {2007} }

TY - JOUR ID - citeulike:4732051 L3 - citeulike-article-id:4732051 N2 - Mitochondrial dysfunction caused by mutations in mitochondrial DNA (mtDNA) is related to a variety of diseases including MELAS and NARP syndromes. However, little is known about the intracellular responses induced by mtDNA mutations. In order to identify genes whose expression is altered as a result of the presence of mtDNA mutations, DNA microarray analysis was performed using human 143B osteosarcoma cells harboring 3243A>G [tRNA-Leu (UUR)] and 8993T>G [ATPase6 Leu156Arg] mtDNA mutations associated with MELAS and NARP syndromes (2SD and NARP3-1 cybrid cells), respectively. We found that mRNA and protein levels of ATF4, CHOP and ASNS were upregulated in 2SD and NARP3-1 cells as compared with parental cells. Reporter assays demonstrated that transcription of CHOP and ASNS genes was upregulated through the AARE (amino acid regulatory element) and NSRE-1 (nutrient-sensing response element-1) enhancer elements to which ATF4 binds, respectively. Furthermore, knockdown of ATF4 by RNA interference reduced CHOP and ASNS transcription in 2SD and NARP3-1 cells. These results suggest that the presence of mtDNA mutations elicits upregulation of CHOP and ASNS genes through the elevation of ATF4 expression and its binding to the AARE and NSRE-1, respectively. IS - 1-2 JF - Mitochondrion SN - 1567-7249 EP - 88 TI - CHOP (C/EBP homologous protein) and ASNS (asparagine synthetase) induction in cybrid cells harboring MELAS and NARP mitochondrial DNA mutations. VL - 7 SP - 80 KW - analysis KW - array KW - human KW - mitochondria KW - narp KW - projnarp AU - Fujita, Y AU - Ito, M AU - Nozawa, Y AU - Yoneda, M AU - Oshida, Y AU - Tanaka, M PY - 2007///r UR - http://dx.doi.org/10.1016/j.mito.2006.11.003 ER -