Remodeling of redox cellular metabolic networks in response to mitochondrial dysfunction

Gyorgy Szabadkai (primary)
Department of Cell and Developmental Biology
University College London, Francis Crick Instititue
Alexandros Kiparissides (secondary)
Department of Biochemical Engineering
University College London

Abstract

Mitochondria are key hubs of cellular redox metabolism, enabling electron flow through the citric acid cycle to the respiratory chain and oxygen as final electron acceptor. Not surprisingly, a large gene network, composed of (i) a significant proportion (>5%) of the nuclear genome and (ii) the small but essential mitochondrial genome, underlies the maintenance of cellular redox balance. The project will focus on understanding the remodeling of the metabolic gene network in response to alterations in the mitochondrial genome and evaluate the functional consequences on metabolic fluxes in central carbon metabolism, by applying transcriptome and metabolic flux analysis and modelling.


References

Bentham,R.B., Bryson,K. and Szabadkai,G. (2017) MCbiclust: a novel algorithm to discover large-scale functionally related gene sets from massive transcriptomics data collections. Nucleic Acids Res., 45, 8712–8730.
Blacker, T. S., Z. F. Mann, J. E. Gale, M. Ziegler, A. J. Bain, G. Szabadkai and M. R. Duchen (2014). “Separating NADH and NADPH fluorescence in live cells and tissues using FLIM.” Nat Commun 5: 3936.
Kiparissides, A., Hatzimanikatis V. (2017). Thermodynamics-based Metabolite Sensitivity Analysis in Metabolic Networks. Metabolic Engineering, v.39, pp: 117-127


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
AgeingBiotechnologyCell BiologyPhysiology
Techniques & Approaches
BiochemistryBioinformaticsGeneticsImage ProcessingMathematics / StatisticsMicroscopy / ElectrophysiologyMolecular BiologySimulation / Modelling