Document Detail

IF1, the endogenous regulator of the F(1)F(o)-ATPsynthase, defines mitochondrial volume fraction in HeLa cells by regulating autophagy.
MedLine Citation:
PMID:  19269273     Owner:  NLM     Status:  MEDLINE    
The protein IF1 limits mitochondrial ATP consumption when mitochondrial respiration is impaired by inhibiting the 'reverse' activity of the F(1)F(o)-ATPsynthase. We have found that IF1 also increases F(1)F(o)-ATPsynthase activity in respiring mitochondria, promoting its dimerization and increasing the density of mitochondrial cristae. We also noted that IF1 overexpression was associated with an increase in mitochondrial volume fraction that was conversely reduced when IF1 was knocked down using small interfering RNA (siRNA). The volume change did not correlate with the level of transcription factors involved in mitochondrial biogenesis. However, autophagy was dramatically increased in the IF1siRNA treated cells (-IF1), assessed by quantifying LC3-GFP translocation to autophagosomes, whilst levels of autophagy were low in IF1 overexpressing cells (+IF1). The increase in LC3-GFP labelled autophagosomes in -IF1 cells was prevented by the superoxide dismutase mimetic, manganese (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP). An increase in the basal rate of generation of reactive oxygen species (ROS) in -IF1 cells was demonstrated using the fluorescent probe dihydroethidium (DHE). Thus, IF1 appears to limit mitochondrial ROS generation, limiting autophagy which is increased by IF1 knockdown. Variations in IF1 expression level may therefore play a significant role in defining both resting rates of ROS generation and cellular mitochondrial content.
Michelangelo Campanella; Andreas Seraphim; Rosella Abeti; Edward Casswell; Pedro Echave; Michael R Duchen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-03-05
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1787     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-11     Completed Date:  2009-07-28     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  393-401     Citation Subset:  IM    
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MeSH Terms
Adenosine Triphosphate / metabolism
Autophagy / physiology*
Cell Death
HeLa Cells / metabolism*
Membrane Potentials / physiology
Mitochondria / enzymology,  physiology,  ultrastructure
Proteins / genetics,  metabolism*
Proton-Translocating ATPases / metabolism*
RNA, Messenger / genetics
Reactive Oxygen Species / metabolism*
Signal Transduction
Transcription Factors / genetics,  metabolism
Grant Support
G0601943//Medical Research Council
Reg. No./Substance:
0/ATPase inhibitory protein; 0/Proteins; 0/RNA, Messenger; 0/Reactive Oxygen Species; 0/Transcription Factors; 8L70Q75FXE/Adenosine Triphosphate; EC ATPases

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