MitoMap, a multi-layered mitochondrial map compiling several levels of molecular interactions
posterposted on 08.09.2017 by jennifer modamio
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Mitochondria are the main energy producers in cells and therefore, mitochondrial dysfunction is commonly associated with a wide range of diseases. In cells with high energetic demands, mitochondria play an essential role in order to maintain this minimum energetic requirement. In some diseases showing dysfunctional mitochondria, such as Parkinson's disease, mutations in signalling proteins are tightly linked to deregulation of metabolic pathways, hence, energy production.
Here, we present the MitoMap, a manually drawn mitochondrial map combining several types of molecular interactions. On the one hand, it compiles all mitochondrial reactions from the latest version of the human metabolic reconstruction, ReconX , accounting for ~1000 mitochondrial reactions. On the other hand, the map also includes manually curated molecular interactions, some of which were extracted from the latest version of the PDmap (http://minerva.uni.lu/MapViewer/). Amongst a wide range of functionalities, the multiscale visualisation of the MitoMap will allow us to specify the amount of information displayed depending on the level of zooming.
Computational predictions from The Constraint-based Reconstruction and Analysis Toolbox (COBRA Toolbox) can also be plotted onto the map, allowing the visualisation of steady state fluxes through the different mitochondrial reactions.
Ongoing work, in the context of the SysMedPD project (http://sysmedpd.eu/) is aimed at computational prediction of mitochondrial targets to slow the progression of neurodegeneration in the subset of Parkinson's disease patients with overt mitochondrial dysfunction. For illustration, here we present an example of the outputs obtained from Parkinson's disease computational models with dysfunctional mitochondria versus control.