# The ABA/LANCL1-2 Hormone/Receptors System Controls ROS Production in Cardiomyocytes through ERRα

## TL;DR

This study shows that the ABA/LANCL1-2 system helps protect heart cells from oxidative stress by controlling ROS through ERRα.

## Contribution

The novel finding is that the ABA/LANCL1-2 system regulates ROS turnover in cardiomyocytes via ERRα, offering a new therapeutic target.

## Key findings

- Overexpression of LANCL1/2 reduces mitochondrial ROS and increases ROS-scavenging enzymes.
- Silencing LANCL1/2 increases ROS and decreases ROS-scavenging enzymes.
- ERRα knockdown eliminates the protective effects of LANCL1/2 overexpression on ROS turnover.

## Abstract

Rat H9c2 cardiomyocytes overexpressing the abscisic acid (ABA) hormone receptors LANCL1 and LANCL2 have an increased mitochondrial proton gradient, respiration, and vitality after hypoxia/reoxygenation. Our aim was to investigate the role of the ABA/LANCL1-2 system in ROS turnover in H9c2 cells. H9c2 cells were retrovirally infected to induce the overexpression or silencing of LANCL1 and LANCL2, without or with the concomitant silencing of the transcription factor ERRα. Enzymes involved in radical production or scavenging were studied by qRT-PCR and Western blot. The mitochondrial proton gradient and ROS were measured with specific fluorescent probes. ROS-generating enzymes decreased, ROS-scavenging enzymes increased, and mitochondrial ROS were reduced in LANCL1/2-overexpressing vs. control cells infected with the empty vector, while the opposite occurred in LANCL1/2-silenced cells. The knockdown of ERRα abrogated all beneficial effects on ROS turnover in LANCL1/2 overexpressing cells. Taken together, these results indicate that the ABA/LANCL1-2 system controls ROS turnover in H9c2 via ERRα. The ABA/LANCL system emerges as a promising target to improve cardiomyocyte mitochondrial function and resilience to oxidative stress.