Master Thesis

DKFZ-2020-02653

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Modulation of intracellular oxygen:making the cell nucleus hypoxic forextracellular oxic conditions

Camazzola, G.DKFZ*

2020

Abstract: In the presented work the analysis of a novel molecular mechanism is proposed, by whichcells can modulate their intracellular oxygen and potentially become hypoxic, inducingfavourable circumstances for metabolic reprogramming, even under extracellular oxic conditions. This phenomenon is based on the competition between O2 diffusion, from theextracellular environment to the nucleus, and its consumption, especially by NOX enzymes.The novelty revolves around the assumptions that the endoplasmic reticulum (ER) membranes can lower the diffusion rate of oxygen, and that the sensing enzymes become moreeffective at removing O2for low values of the Michaelis constant KM. After a preliminarystudy of oxygen concentration inside the cell, an analysis of different factors affecting thisphenomenon was carried out. Attention was given to the Michaelis-Menten parametersVmax and KM, considering consumption differences between ER and cytosol, the extracellular oxygen, the number of membrane pairs, the membrane porosity and the dependence onthe cell cycle phase. A relation between porosity and number of membranes was established,and the ratio of nuclear O2 of G1 phase relative to S phase, for different KM, was determined. In conclusion, the initial hypothesis has been confirmed, and some experimentalresults obtained in previous studies have been validated.

Note: Masterarbeit, Universität Heidelberg, 2020

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Contributing Institute(s):

1. E041 Medizinische Physik in der Radioonkologie (E041)

Research Program(s):

1. 315 - Imaging and radiooncology (POF3-315) (POF3-315)

Appears in the scientific report 2020

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