Document Detail

Decreased expression of Drp1 and Fis1 mediates mitochondrial elongation in senescent cells and enhances resistance to oxidative stress through PINK1.
MedLine Citation:
PMID:  20179104     Owner:  NLM     Status:  MEDLINE    
Mitochondria display different morphologies, depending on cell type and physiological situation. In many senescent cell types, an extensive elongation of mitochondria occurs, implying that the increase of mitochondrial length in senescence could have a functional role. To test this hypothesis, human endothelial cells (HUVECs) were aged in vitro. Young HUVECs had tubular mitochondria, whereas senescent cells were characterized by long interconnected mitochondria. The change in mitochondrial morphology was caused by downregulation of the expression of Fis1 and Drp1, two proteins regulating mitochondrial fission. Targeted photodamage of mitochondria induced the formation of reactive oxygen species (ROS), which triggered mitochondrial fragmentation and loss of membrane potential in young cells, whereas senescent cells proved to be resistant. Alterations of the Fis1 and Drp1 expression levels also influenced the expression of the putative serine-threonine kinase PINK1, which is associated with the PARK6 variant of Parkinson's disease. Downregulation of PINK1 or overexpression of a PINK1 mutant (G309D) increased the sensitivity against ROS in young cells. These results indicate that there is a Drp1- and Fis1-induced, and PINK1-mediated protection mechanism in senescent cells, which, when compromised, could contribute to the age-related progression of Parkinson's disease and arteriosclerosis.
Sören Mai; Michael Klinkenberg; Georg Auburger; Jürgen Bereiter-Hahn; Marina Jendrach
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-23
Journal Detail:
Title:  Journal of cell science     Volume:  123     ISSN:  1477-9137     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-04     Completed Date:  2010-06-15     Revised Date:  2012-06-19    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  917-26     Citation Subset:  IM    
Kinematic Cell Research Group, Institute for Cell Biology and Neuroscience, Center of Excellence Frankfurt: Macromolecular Complexes, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt/Main, Germany.
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MeSH Terms
Cell Aging* / radiation effects
Endothelial Cells / cytology*,  enzymology,  radiation effects
GTP Phosphohydrolases / metabolism*
Gene Expression Regulation, Enzymologic / radiation effects
Membrane Proteins / metabolism*
Microtubule-Associated Proteins / metabolism*
Mitochondria / enzymology*,  pathology,  radiation effects
Mitochondrial Proteins / metabolism*
Models, Biological
Oxidative Stress* / radiation effects
Protein Kinases / genetics,  metabolism*
RNA, Messenger / genetics,  metabolism
Reactive Oxygen Species / metabolism
Umbilical Veins / cytology
Up-Regulation / radiation effects
Reg. No./Substance:
0/FIS1 protein, human; 0/Membrane Proteins; 0/Microtubule-Associated Proteins; 0/Mitochondrial Proteins; 0/RNA, Messenger; 0/Reactive Oxygen Species; EC 2.7.-/Protein Kinases; EC putative kinase; EC 3.6.1.-/GTP Phosphohydrolases; EC protein, human

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