A minimal titration modelization of the mammalian dynamical heat shock response

TL;DR

This paper presents a minimal mathematical model of the mammalian heat shock response, capturing key dynamics and revealing how chaperone titration, protein triage, and temperature regimes govern cellular stress responses.

Contribution

It introduces a simplified yet effective model that reproduces experimental data and elucidates core mechanisms of the heat shock response network.

Findings

Chaperone titration of HSF1 is central to the response.

Protein triage determines damaged protein fate.

Three temperature regimes describe different stress levels.

Abstract

Environmental stress, such as oxidative or heat stress, induces the activation of the Heat Shock Response (HSR) which leads to an increase in the heat shock proteins (HSPs) level. These HSPs act as molecular chaperones to maintain proteostasis. Even if the main heat shock response partners are well known, a detailed description of the dynamical properties of the HSR network is still missing. In this study, we derive a minimal mathematical model of cellular response to heat shock that reproduces available experimental data sets both on transcription factor activity and cell viability. This simplistic model highlights the key mechanistic processes that rule the HSR network and reveals (i) the titration of Heat Shock Factor 1 (HSF1) by chaperones as the guiding line of the network, (ii) that protein triage governs the fate of damaged proteins and (iii) three different temperature regimes describing normal, acute or chronic stress.