PhD Scientific Days 2024

Budapest, 9-10 July 2024

Molecular Medicine II.

In silico investigation of the dual role of autophagy


Bence Hajdú1, Tibor Nagy2, Orsolya Kapuy1
1: Department of Molecular Biology Semmelweis University, Institute of Biochemistry and Molecular Biology
2: Institute of Materials and Environmental Chemistry Hungarian Research Network

Text of the abstract

Autophagy is an evolutionarily conserved dynamic catabolic process in eukaryotic cells, where doublemembrane vesicles containing cytoplasmic components are
formed and degraded in specialized vesicles. It primarily influences cell survival by maintaining the cell's energy balance and degrading damaged macromolecules and
organelles. However, due to it being tightly connected to apoptosis, autophagy can also promote cell death. Consequently, the modulation of autophagy plays dual roles
in tumor cells, both promoting and suppressing tumor proliferation. To better understand this nature of autophagy we made a chemical reaction kinetics model of
autophagy and apoptosis. The initial model was made by Bing Liu [1]. It is a mass action kinetic model containing 94 species, 119 reactions and 129 parameters. They
only used one data set for the parameter estimation and initial conditions for the species were not provided also as well. Therefore the model cannot be used for general
simulations. To further develop the model realistic initial value conditions were given for each species. Then the model was optimized with the Optima++ software
package. A new parameter set was estimated with our group’s previously published data to estimate the parameters and validate the model [2,3]. The improved model
is able to track the concentration changes in time of several regulatory proteins with reasonable accuracy, making the model usable for in silico investigation of autophagy
related diseases. Supported by the ÚNKP233II new National Excellence Program of the Ministry for Culture and Innovation from the sources of the National
Research, Development and Innovation Fund.