Park 2015 Proc Natl Acad Sci USA: Difference between revisions
(Created page with "{{Publication |title=Park JH, Kang HJ, Lee YK, Kang H, Kim J, Chung JH, Chang JS, McPherron AC, Lee SB (2015) Inactivation of EWS reduces PGC-1ฮฑ protein stability and mitochondr...") ย |
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{{Publication | {{Publication | ||
|title=Park JH, Kang HJ, Lee YK, Kang H, Kim J, Chung JH, Chang JS, McPherron AC, Lee SB (2015) Inactivation of EWS reduces PGC-1ฮฑ protein stability and mitochondrial homeostasis. Proc Natl Acad Sci USA 112:6074-9. ย | |title=Park JH, Kang HJ, Lee YK, Kang H, Kim J, Chung JH, Chang JS, McPherron AC, Lee SB (2015) Inactivation of EWS reduces PGC-1ฮฑ protein stability and mitochondrial homeostasis. Proc Natl Acad Sci USA 112:6074-9. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/25918410 PMID: 25918410] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/25918410 PMID: 25918410] | ||
|authors=Park JH, Kang HJ, Lee YK, Kang H, Kim J, Chung JH, Chang JS, McPherron AC, Lee SB | |authors=Park JH, Kang HJ, Lee YK, Kang H, Kim J, Chung JH, Chang JS, McPherron AC, Lee SB | ||
|year=2015 | |year=2015 | ||
|journal=Proc Natl Acad Sci USA | |journal=Proc Natl Acad Sci USA | ||
|abstract=EWS (Ewing sarcoma) encodes an RNA/ssDNA binding protein that is frequently rearranged in a number of different cancers by chromosomal translocations. Physiologically, EWS has diverse and essential roles in various organ development and cellular processes. In this study, we uncovered a new role of EWS in mitochondrial homeostasis and energy metabolism. Loss of EWS leads to a significant decrease in mitochondria abundance and activity, which is caused by a rapid degradation of Peroxisome proliferator-activated receptor ฮณ Coactivator (PGC-1ฮฑ), a central regulator of mitochondria biogenesis, function, and cellular energy metabolism. EWS inactivation leads to increased ubiquitination and proteolysis of PGC-1ฮฑ via proteasome pathway. Complementation of EWS in Ews-deficient cells restores PGC-1ฮฑ and mitochondrial abundance. We found that expression of E3 ubiquitin ligase, FBXW7 (F-box/WD40 domain protein 7), is increased in the absence of Ews and depletion of Fbxw7 in Ews-null cells restores PGC-1ฮฑ expression and mitochondrial density. Consistent with these findings, mitochondrial abundance and activity are significantly reduced in brown fat and skeletal muscles of Ews-deficient mice. Furthermore, expression of mitochondrial biogenesis, respiration and fatty acid ฮฒ-oxidation genes is significantly reduced in the liver of Ews-null mice. These results demonstrate a novel role of EWS in mitochondrial and cellular energy homeostasis by controlling PGC-1ฮฑ protein stability, and further implicate altered mitochondrial and energy metabolism in cancers harboring the EWS translocation. ย | |abstract=EWS (Ewing sarcoma) encodes an RNA/ssDNA binding protein that is frequently rearranged in a number of different cancers by chromosomal translocations. Physiologically, EWS has diverse and essential roles in various organ development and cellular processes. In this study, we uncovered a new role of EWS in mitochondrial homeostasis and energy metabolism. Loss of EWS leads to a significant decrease in mitochondria abundance and activity, which is caused by a rapid degradation of Peroxisome proliferator-activated receptor ฮณ Coactivator (PGC-1ฮฑ), a central regulator of mitochondria biogenesis, function, and cellular energy metabolism. EWS inactivation leads to increased ubiquitination and proteolysis of PGC-1ฮฑ via proteasome pathway. Complementation of EWS in Ews-deficient cells restores PGC-1ฮฑ and mitochondrial abundance. We found that expression of E3 ubiquitin ligase, FBXW7 (F-box/WD40 domain protein 7), is increased in the absence of Ews and depletion of Fbxw7 in Ews-null cells restores PGC-1ฮฑ expression and mitochondrial density. Consistent with these findings, mitochondrial abundance and activity are significantly reduced in brown fat and skeletal muscles of Ews-deficient mice. Furthermore, expression of mitochondrial biogenesis, respiration and fatty acid ฮฒ-oxidation genes is significantly reduced in the liver of Ews-null mice. These results demonstrate a novel role of EWS in mitochondrial and cellular energy homeostasis by controlling PGC-1ฮฑ protein stability, and further implicate altered mitochondrial and energy metabolism in cancers harboring the EWS translocation. | ||
|keywords=EWS, PGC-1alpha, Energy metabolism, Mitochondria homeostasis, Protein stability | |keywords=EWS, PGC-1alpha, Energy metabolism, Mitochondria homeostasis, Protein stability, Adipocyte | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration | |area=Respiration, Genetic knockout;overexpression | ||
|organism=Mouse | |organism=Mouse | ||
|tissues= | |tissues=Fat | ||
|preparations=Intact cells | |preparations=Intact cells | ||
|diseases=Cancer | |diseases=Cancer | ||
| Line 17: | Line 17: | ||
|substratestates=ROX | |substratestates=ROX | ||
|instruments=Oxygraph-2k, O2k-Manual | |instruments=Oxygraph-2k, O2k-Manual | ||
}} | }} | ||
Revision as of 15:54, 24 March 2016
| Park JH, Kang HJ, Lee YK, Kang H, Kim J, Chung JH, Chang JS, McPherron AC, Lee SB (2015) Inactivation of EWS reduces PGC-1ฮฑ protein stability and mitochondrial homeostasis. Proc Natl Acad Sci USA 112:6074-9. |
Park JH, Kang HJ, Lee YK, Kang H, Kim J, Chung JH, Chang JS, McPherron AC, Lee SB (2015) Proc Natl Acad Sci USA
Abstract: EWS (Ewing sarcoma) encodes an RNA/ssDNA binding protein that is frequently rearranged in a number of different cancers by chromosomal translocations. Physiologically, EWS has diverse and essential roles in various organ development and cellular processes. In this study, we uncovered a new role of EWS in mitochondrial homeostasis and energy metabolism. Loss of EWS leads to a significant decrease in mitochondria abundance and activity, which is caused by a rapid degradation of Peroxisome proliferator-activated receptor ฮณ Coactivator (PGC-1ฮฑ), a central regulator of mitochondria biogenesis, function, and cellular energy metabolism. EWS inactivation leads to increased ubiquitination and proteolysis of PGC-1ฮฑ via proteasome pathway. Complementation of EWS in Ews-deficient cells restores PGC-1ฮฑ and mitochondrial abundance. We found that expression of E3 ubiquitin ligase, FBXW7 (F-box/WD40 domain protein 7), is increased in the absence of Ews and depletion of Fbxw7 in Ews-null cells restores PGC-1ฮฑ expression and mitochondrial density. Consistent with these findings, mitochondrial abundance and activity are significantly reduced in brown fat and skeletal muscles of Ews-deficient mice. Furthermore, expression of mitochondrial biogenesis, respiration and fatty acid ฮฒ-oxidation genes is significantly reduced in the liver of Ews-null mice. These results demonstrate a novel role of EWS in mitochondrial and cellular energy homeostasis by controlling PGC-1ฮฑ protein stability, and further implicate altered mitochondrial and energy metabolism in cancers harboring the EWS translocation. โข Keywords: EWS, PGC-1alpha, Energy metabolism, Mitochondria homeostasis, Protein stability, Adipocyte
Labels: MiParea: Respiration, Genetic knockout;overexpression
Pathology: Cancer
Organism: Mouse Tissue;cell: Fat Preparation: Intact cells
Coupling state: LEAK, ROUTINE, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.
HRR: Oxygraph-2k, O2k-Manual
