Tour-de-Force

Tour-de-Force: Interplay between Mitochondria and Cell Cycle Progression Fall 2007The generation of metabolic activity, mainly enabled by the mitochondria, is a major activity of allcells. Most energy in the cell is obtained from oxydative phosphorylation within the mitochondria. Duringoxidative phosphorylation, electrons stemming from NADH and FADH2 combine with oxygen. Theelectron transport chain uses the energy released from oxidation/reduction reactions to firstly produce aproton gradient across the inner mitochondrial membrane. In the process of chemiosmosis, protons flowback across the membrane in order to produce ATP from ADP (Figure 2).Figure 2 Oxidative Phosphorylationcreates energy through the electrontransport chain and chemiosmosisSource: Oxidation-Reduction Reactions andProton Pumping in Oxidative Phosphorylation;http://www.chemistry.wustl.edu/~courses/genchem/Tutorials/Cytochrome/ProtonPump.htmAs the mitochondria are the main suppliers of energy within the cell, and all cellular processesrequire energy, it naturally follows that mitochondrial activity has great influence on the cell as a whole.Furthermore, as a byproduct of oxidative phosphorylation, radical oxygen species are produced that havegreat impact within the cell as well. Through the production of these molecules, mitochondria are believedto also have a regulative influence on cell cycle progression.Mitochondria have been shown to be very dynamic organelles. They are known to fuse and divideagain, and it remains relatively unclear what the function of these processes is. The most popularhypothesis at this moment is that the fusion and fission of mitochondria ensures that the mitochondrialgenetic information is distributed evenly over all mitochondria, which might be necessary after mutations.Additionally, various mitochondrial proteins are transcribed in the nucleus. Furthermore, cell cycleproteins have been proven to affect the mitochondria directly in several ways. Therefore it is believed thatthe cell cycle and cell cycle progression highly influence mitochondrial activity, morphology and biogenesis.Cell cycle and mitochondrial activity: making the linkAccording to the widely accepted principle of endosymbiosis, mitochondria started off as onesingle bacterium that was taken up by another, larger, cell. This makes mitochondria remarkableorganelles having their own genetic information and being able to divide independently from their host cell.However, over the course of time, the bacterium and the larger cell have been becoming increasinglydependent of each other. Nowadays, in animal cells, mitochondria still have their own genetic system,although not all mitochondrial proteins are encoded by this internal genome. Mitochondria therefore arehighly influenced by the general transcription of proteins in the nucleus, and communication is known totake place between the nucleus and mitochondria. Because of their extraordinary origin, thiscommunication between the nucleus and mitochondria is a very important example of the creativity ofevolution. It clearly demonstrates how systems evolved to form a better functioning system. It has beenproposed that the two regulate each other’s activity in various ways. This research proposal aims to give amore complete overview of the communication between two of the most important cellular aspects: thecell cycle, allowing the cell grow and to divide, and the mitochondria, once an organism itself.This research proposal focuses on the various regulative influences that the mitochondria have onthe cell cycle and cell cycle progression. Additionally, several propositions are made on the regulative roleSCI 332 Advanced Molecular Cell Biology Research Proposal 6