Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Abscisic Acid and Its Receptors LANCL1 and LANCL2 Control Cardiomyocyte Mitochondrial Function, Expression of Contractile, Cytoskeletal and Ion Channel Proteins and Cell Proliferation via ERRα

Sonia Spinelli
* ORCID logo ,
Lucrezia Guida
,
Mario Passalacqua
ORCID logo ,
Mirko Magnone
,
Vanessa Cossu
,
Gianmario Sambuceti
ORCID logo ,
Cecilia Marini
,
Laura Sturla
* ORCID logo ,
Elena Zocchi
*
Version 1 : Received: 1 August 2023 / Approved: 2 August 2023 / Online: 3 August 2023 (10:36:44 CEST)

A peer-reviewed article of this Preprint also exists.

Spinelli, S.; Guida, L.; Passalacqua, M.; Magnone, M.; Cossu, V.; Sambuceti, G.; Marini, C.; Sturla, L.; Zocchi, E. Abscisic Acid and Its Receptors LANCL1 and LANCL2 Control Cardiomyocyte Mitochondrial Function, Expression of Contractile, Cytoskeletal and Ion Channel Proteins and Cell Proliferation via ERRα. Antioxidants 2023, 12, 1692. Spinelli, S.; Guida, L.; Passalacqua, M.; Magnone, M.; Cossu, V.; Sambuceti, G.; Marini, C.; Sturla, L.; Zocchi, E. Abscisic Acid and Its Receptors LANCL1 and LANCL2 Control Cardiomyocyte Mitochondrial Function, Expression of Contractile, Cytoskeletal and Ion Channel Proteins and Cell Proliferation via ERRα. Antioxidants 2023, 12, 1692.

Abstract

The cross-kingdom stress hormone abscisic acid (ABA) and its mammalian receptors LANCL1 and LANCL2 regulate cardiomyocyte response to hypoxia by activating NO generation. Over-expression of LANCL1/2 increases transcription, phosphorylation and activity of eNOS and im-proves cell vitality after hypoxia/reoxygenation via the AMPK/PGC-1α axis. The aim of this study was to investigate whether the ABA/LANCL system also affects mitochondrial oxidative metab-olism and structural proteins. The effect of ABA and of the silencing or overexpression of LANCL1 and LANCL2 were investigated in H9c2 rat cardiomyoblasts on mitochondrial function, cell cycle and expression of cytoskeletal, contractile and ion channel proteins. Overexpression or silencing of LANCL1/2 significantly increased, or conversely decreased, mitochondrial number, oxphos complex I, proton gradient, glucose and palmitate-dependent respiration, transcription of uncoupling proteins, expression of proteins involved in cytoskeletal, contractile and electrical functions. These effects, and LANCL1/2-dependent NO generation, are mediated by the tran-scription factor ERRα, upstream of the AMPK/PGC1-α axis and transcriptionally controlled by the LANCL1/2-ABA system. The ABA-LANCL1/2 hormone-receptors system controls fundamental aspects of cardiomyocyte physiology via an ERRα/AMPK/PGC-1α signaling axis and ABA-mediated targeting of this axis could improve cardiac function and resilience to hypoxic and dysmetabolic conditions.

Keywords

mitochondrial function; cell cycle; cardiomyocyte functional proteins; proton leak.

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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