Tour-de-Force

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Tour-de-Force: Interplay between Mitochondria and Cell Cycle Progression Fall 2007Zhou et al., (2001), “Role of AMP-Activated Protein Kinase in mechanism of metformin action”, The Journal of Clinical Investigation,108, 1167-1174.WebsitesAbcam, Cambridge, catalogue for antibodies, www.abcam.com. Consulted on Thursday November 29 th 2007.Amaxa Biosystems, Maryland, catalogue for cell lines, www.amaxa.com. Consulted on Thursday November 29 th 2007.Cellular Technology Ltd., Shaker Heights, 2007, accessed 27 November 2007, http://www.immunospot.com/index.php?id=1Evrogen, Moscow, 2007, accessed 15 November 2007, Istituto Nazionale per la Ricerca sul Cancro: Cell Line Data Base, Genova, 2007, accessed 24 November 2007,Molecular Modeling by Dyck, R.B., and Lopaschuk, G.D. "AMPK Alterations in Cardiac Physiology and Pathology: Enemy or Ally"http://www.bioon.com/book/biology/genomicglossaries/molecular_modeling_gloss.asp.htmSanta Cruz Biotechnology Inc., 2007, accessed 27 November 2007, http://www.scbt.com/index.htmlWebsite for: Aging research; molecular concepts of aging and related diseases and cloning,http://www.innovitaresearch.org/news/04112901.htmlSCI 332 Advanced Molecular Cell Biology Research Proposal 56

Tour-de-Force: Interplay between Mitochondria and Cell Cycle Progression Fall 2007Mitochondrial Biogenesis during the Cell CycleInvestigating interactions of the PPAR family coactivators in the induction ofmitochondrial biogenesis in coordination with the cell cycle through regulation of NRF-1activityResearch Proposal byB.B.F. Eidhof, I. Flament, S.L. Giles, J. Gunkel, W.P. van Klinken, J.A.J.M. PijnenburgAbstractThe cell is a very dynamic and intricate system comprised of a vast array of intracellular components. Amongthese components are the mitochondria, which in broad terms are the master energy providers for cellularfunctions. Mitochondria have long been a topic of fascination in the world of molecular biology. A vastplethora of diseases are attributed to the dysfunction of these crucial organelles that provide cells with energy.Mitochondria are present in multiple copies in the cell and are usually arranged in an elongated tubularnetwork. An important aspect of mitochondria is their biogenesis, which subsumes various processesconcerned with growth of organelles, energy, as well as being an important preparatory measure for cell cycleprogression and mitosis. The Peroxisome Proliferator Activated Gamma Coactivator (PPAR) family proteinsare the master regulatory components that induce mitochondrial biogenesis. They act to induce biogenesis byassociating with Nuclear Respiratory Factor (NRF), which in return is able to activate gene expression ofvarious mitochondrial components. On the other hand, cyclin D appears to inhibit NRF activity. In theproposed research, these two pathways upstream of NRF will be put under scrutiny, to elucidate themechanism that links mitochondrial biogenesis and the cell cycle. Although a lot of research has beendedicated to mitochondrial biogenesis, the details of how this process is activated in quiescent cells enteringthe cell cycle as well as continuously proliferating cells, are still unclear. Therefore, the main aim of thisresearch is to investigate the dynamics of mitochondrial biogenesis during the cell cycle and how thesevarious processes that induce mitochondrial biogenesis may be coordinated.SCI 332 Advanced Molecular Cell Biology Research Proposal 57

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