Preprint Article Version 1 This version is not peer-reviewed

The Switching of the Type of a ROS Signal from Mitochondria: The Role of Respiratory Substrates and Permeability Transition

Version 1 : Received: 30 September 2024 / Approved: 1 October 2024 / Online: 3 October 2024 (08:31:25 CEST)

How to cite: Kruglov, A. G.; Nikiforova, A. B. The Switching of the Type of a ROS Signal from Mitochondria: The Role of Respiratory Substrates and Permeability Transition. Preprints 2024, 2024100024. https://doi.org/10.20944/preprints202410.0024.v1 Kruglov, A. G.; Nikiforova, A. B. The Switching of the Type of a ROS Signal from Mitochondria: The Role of Respiratory Substrates and Permeability Transition. Preprints 2024, 2024100024. https://doi.org/10.20944/preprints202410.0024.v1

Abstract

Flashes of superoxide anion (SA) in mitochondria are generated spontaneously or during the opening of the permeability transition pore (PTP) and a sudden change in the metabolic state of a cell. Under certain conditions, SA can leave the mitochondrial matrix and perform signaling functions beyond mitochondria. In this work, we studied the kinetics of the release of SA and H2O2 from isolated mitochondria upon PTP opening and the modulation of the metabolic state of mitochondria by the substrates of respiration and oxidative phosphorylation. It was found that PTP opening leads to suppression of H2O2 emission and activation of SA burst. When the induction of PTP was blocked by its antagonists (cyclosporine A, ruthenium red, EGTA), the level of substrates of respiration and oxidative phosphorylation and the selective inhibitors of complexes I and V determined the type of ROS emitted by mitochondria. It was concluded that upon complete and partial reduction and complete oxidation of redox centers of the respiratory chain, mitochondria emit H2O2, SA, and nothing, respectively. The results indicate that the PTP- and substrate-dependent switching of the type of ROS leaving mitochondria may be the basis for SA- and H2O2-selective redox signaling in a cell.

Keywords

mitochondria; superoxide anion; hydrogen peroxide; kinetics; redox signaling; OXPHOS substrates

Subject

Biology and Life Sciences, Biophysics

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.