Tour-de-Force

13.07.2015 Views
Tour-de-Force: Interplay between Mitochondria and Cell Cycle Progression Fall 2007Puigserver, P. and Spiegelman, B.M. (2003) “Peroxisome Proliferator-Activated Receptor – γ Coactivator 1α (PGC-1α): TranscriptionalCoactivator and Metabolic Regulator” Endocrine Reviews 24, 78-90Reznick, R. and Shulman, G.I. (2006) “The role of AMP-activated protein kinase in mitochondrial biogenesis” The Journal of Physiology,574, 33-39Sonoda, J. et. al., (2007) “PGC-1β controls mitochondrial metabolism to modulate circadian activity, adaptive thermogenesis, andhepatic steatosis” Proc Natl Acad Sci U.S.A. 104, 5223–5228.Taanman, J.W. et. al. (1997) “Molecular mechanisms in mitochondrial DNA depletion syndrome” Human Molecular Genetics 6, 935-942Van den Bogert, C. et. al. (1988) “Mitochondrial Biogenesis and Mitochondrial Activity during the Progression of the Cell Cycle ofHuman Leukemic Cells” Experimental Cell Research 178, 143-153Vercauteren, K. et. al. (2006) “PGC-1-related coactivator (PRC): immediate early expression and characterization of a CREB/NRF-1binding domain associated with cytochrome c promoter occupancy and respiratory growth” Mol Cell Biology 20, 7409-7419Virbasius and Scarpulla (1994) “Activation of the human mitochondrial transcription factor A gene by nuclear respiratory factors: apotential regulatory link between nuclear and mitochondrial gene expression in organelle biogenesis” Proc. Natl. Acad. Sci. 91(4),1309-1313Wackerhage, H. et. al, (2002) “Exercise-induced Signal Transduction and Gene Regulation in Skeletal Muscle” Journal of SportsScience and Medicine 1, 103-114Wang C., et al., (2006), Cyclin D1 repression of nuclear respiratory factor 1 integrates nuclear DNA synthesis and mitochondrialfunction, PNAS, 103, 11567-11572.Wulf, A. et. al. (2007) “T3-mediated gene expression is independent of PGC-1α” Molecular and Cellular Endocrinology 270, 57-63Zoltan, A., et. al. (2007) “The Transcriptional Coactivator PGC-1β Drives the Formation of Oxidative Type IIX Fibers in SkeletalMuscle” Cell Metabolism 5, 35-46SCI 332 Advanced Molecular Cell Biology Research Proposal 72

Tour-de-Force: Interplay between Mitochondria and Cell Cycle Progression Fall 2007Mitofusin 2 and the Cell CycleA role for Mitofusin 2 in the regulative interaction between mitochondria and cell cycleprogressionResearch proposal byJ. Claus, S.J.H. Diederen, L. Hussaarts, S. Kamps, A. Moussa, A. SchierenbergAbstractMitofusins play a crucial role in the fusion machinery of mitochondria. Mitofusin-2 (Mfn2) contributes tofusion, but has additional roles as well. Overexpression of the protein causes an upregulation of OXPHOS,which results in a higher mitochondrial membrane potential. Mfn2 is also able to bind to Ras, which leadsto inhibition of the Raf-MEK-ERK pathway, resulting in cell cycle arrest or apoptosis. It is striking that oneprotein can have such contradictory functions in the cell. Little is known about these functions of Mfn2,especially when it comes to the protein’s role in cell cycle progression and normal cellular functioning.Recent discoveries of two isoforms of Mfn2 – a lighter and a heavier one – provided new insights on howMfn2 can play a role in both pathways. To investigate these isoforms with their different roles andespecially in relation to the cell cycle, this research proposes firstly measuring the Mfn2 levels throughoutthe different phases of the cell cycle. Subsequently, it will be investigated how Mfn2 influences OXPHOSin addition to examining the role of Stomatin-like Protein 2 (Stoml2) in this process. Moreover, it will beexplored whether the lighter isoform of Mfn2 is restricted to the cytosol, and whether this isoform iscreated through cleavage of a specific part of the heavier isoform, which suggested to be localized in themitochondria. Furthermore, it will be studied whether cytosolic Mfn2 fluctuates throughout the cell cycleand whether oxidative stress leads to higher expression of this cytosolic form. It will be researchedwhether Ras mediated cell cycle arrest is induced when Mfn2 reaches a certain threshold. Finally anexploration of the correlation between cyclins and Mfn2 is proposed, to explore whether cyclins play a rolein influencing Mfn2 production or activity.SCI 332 Advanced Molecular Cell Biology Research Proposal 73

Page 1 and 2: Tour-de-ForceInterplay between mito

Page 3 and 4: Tour-de-Force: Interplay between Mi


































Page 71: Tour-de-Force: Interplay between Mi























cycle

mitochondrial

levels

mitochondria

progression

ampk

cyclin

molecular

biology

protein

Tour-de-Force

Tour-de-Force ... View more Tour-de-Force

Delete template?

Save as template ?

Tour-de-Force Tour-de-Force