Work

Revealing the Deactivation Mechanism of Aconitase at the Atomistic Level by Multiscale Simulations

Year: 2026

Type: preprint

Abstract: Mitochondrial aconitase is a key enzyme of the citric acid cycle that converts citrate to isocitrate at its [4 Fe−4 S] cluster cofactor. It is widely conserved across vertebrates and also found in numerous other organisms. Oxidation of the [4 Fe−4 S] cluster by reactive oxygen and nitrogen species (ROS/RNS) leads to the release of one Fe center, denoted as Fe α . The remaining [3 Fe−4 S] cluster is catalytically inactive, meaning aconitase oxidation leads to enzyme deactivation. Aconitase deactivation regulates the citric acid cycle and mitochondrial respiration, which leads to decreased ROS and RNS formation. Thus, aconitase serves as a redox sensor that prevents high ROS and RNS concentrations. The deactivation process is well characterized on the macroscopic scale, meaning that the deactivation kinetics and the thermodynamics of oxidation are known.

Source: ChemRxiv

DOI: 10.26434/chemrxiv.15009474/v1

Authors: Michael Stier, Kristyna Pluhackova, Johannes Kästner

Institutions: University of Stuttgart, Stuttgart Center for Simulation Science

Language: English

Topic: Metalloenzymes and iron-sulfur proteins

Subfield: Biochemistry

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: Deutsche Forschungsgemeinschaft, Singapore Institute of Manufacturing Technology

OpenAlex ID: W7214392742

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