| Mitochondrial dysfunction by complex II inhibition delays overall cell cycle progression via reactive oxygen species production. | |
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MedLine Citation:
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PMID: 18395845 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mitochondrial complex II defect has recently been implicated in cellular senescence and in the ageing process of which a critical phenotype is retardation and arrest of cellular growth. However, the underlying mechanisms of how complex II defect affects cellular growth, remain unclear. In this study, we investigated the effect of complex II inhibition using a subcytotoxic dose (400 microM) of 2-thenoyltrifluoroacetone (TTFA), a conventional complex II inhibitor, on cell cycle progression. TTFA (400 microM) directly decreased KCN-sensitive cellular respiration rate to 67% of control and disrupted the mitochondrial membrane potential. In contrast to other respiratory inhibitors such as rotenone, antimycin A, and oligomycin, TTFA prolonged the duration of each phase of the cell cycle (G1, S, and G2/M) equally, thereby delaying overall cell cycle progression. This delay was accompanied by a biphasic increase of reactive oxygen species (ROS) and concurrent glutathione oxidation, in addition to a slight decrease in the cellular ATP level. Finally, the delay in cell cycle progression caused by TTFA was proved to be mainly due to ROS overproduction and subsequent oxidative stress, as evidenced by its reversal following pretreatment with antioxidants. Taken together, these results suggest that an overall delay in cell cycle progression due to complex II defects may contribute to ageing and degenerative diseases via inhibition of cellular growth and proliferation without arrest at any specific phase of the cell cycle. |
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Authors:
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Hae-Ok Byun; Hee Young Kim; Jin J Lim; Yong-Hak Seo; Gyesoon Yoon |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cellular biochemistry Volume: 104 ISSN: 1097-4644 ISO Abbreviation: J. Cell. Biochem. Publication Date: 2008 Aug |
Date Detail:
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Created Date: 2008-07-28 Completed Date: 2008-10-17 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 8205768 Medline TA: J Cell Biochem Country: United States |
Other Details:
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Languages: eng Pagination: 1747-59 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 443-721, South Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism Cell Cycle* / drug effects Cell Death / drug effects Cell Line Cell Proliferation / drug effects Cyclin-Dependent Kinase Inhibitor p21 / metabolism Electron Transport Complex II / antagonists & inhibitors* Glucose / pharmacology Intracellular Space / drug effects, metabolism Mitochondria / drug effects, enzymology*, pathology*, ultrastructure Oxidative Stress / drug effects Reactive Oxygen Species / metabolism* Thenoyltrifluoroacetone / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Cyclin-Dependent Kinase Inhibitor p21; 0/Reactive Oxygen Species; 326-91-0/Thenoyltrifluoroacetone; 50-99-7/Glucose; 56-65-5/Adenosine Triphosphate; EC 1.3.5.1/Electron Transport Complex II |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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