Reference : Modeling cellular ROS defense in mitochondrial-related diseases

	Document type :	Scientific congresses, symposiums and conference proceedings : Poster
	Discipline(s) :	Life sciences : Multidisciplinary, general & others
	Focus Areas :	Computational Sciences
	To cite this reference:	http://hdl.handle.net/10993/5763

Title :	Modeling cellular ROS defense in mitochondrial-related diseases
Language :	English
Author, co-author :	Simeonidis, Vangelis [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
	Kolodkin, Alexey [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
	Ignatenko, Andrew [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Engineering Research Unit >]
	Sangar, Vineet []
	Balling, Rudi [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
	Brady, Nathan []
Publication date :	22-Jul-2013
Peer reviewed :	Yes
On invitation :	No
Audience :	International
Event name :	21st Annual International Conference on Intelligent Systemsfor Molecular Biology and 12th European Conference on Computational Biology
Event date :	21-23 July 2013
Event organizer :	International Society for Computational Biology
Event place (city) :	Berlin
Event country :	Germany
Abstract :	[en] Reactive Oxygen Species (ROS) generation is an unavoidable background process during normal cellular function. The main contributor to ROS production is the electron transport chain, which reduces oxygen to water. Some incompletely-reduced oxygen species escape and oxidize a variety of organic molecules, leading to molecular dysfunction and initiating a positive feedback loop of ever increasing active radical production. The increased concentration of ROS damages the mitochondria, therefore further elevating the rate of ROS generation. Healthy cells manage ROS enzymatically and by mitophagy of damaged mitochondria. The precise tuning of the latter mechanism is crucial for cell survival and is controlled by a ROS-induced regulatory network. We have built a set of kinetic models of varying complexity, based on the current understanding of the mechanism of cellular ROS defense. Our models allow simulation of various patho-physiological scenarios related to mitochondrial dysfunction and the failure of the system of ROS regulation in human cells. We employ the models we have constructed to simulate the effects of diseases related to mitochondrial dysfunction and excessive ROS generation, such as Parkinson’s disease, Huntington’s disease and cancer. Experimental evidence is used for model fitting, and we propose model improvements based on incorporation of single-cell experimental measurements. Finally, we discuss the perspective of integrating our kinetic models with genome-scale, constraint-based, tissue-specific models of metabolism, in order to study the effect of ROS misregulation on metabolic phenotype.
Research centres :	Luxembourg Centre for Systems Biomedicine
Target :	Researchers
Permalink :	http://hdl.handle.net/10993/5763

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