Peugnet 2022 Antioxidants (Basel)

From Bioblast
Publications in the MiPMap
Peugnet V, Chwastyniak M, Mulder P, Lancel S, Bultot L, Fourny N, Renguet E, Bugger H, Beseme O, Loyens A, Heyse W, Richard V, Amouyel P, Bertrand L, Pinet F, Dubois-Deruy E (2022) Mitochondrial-targeted therapies require mitophagy to prevent oxidative stress induced by SOD2 inactivation in hypertrophied cardiomyocytes.

Β» Antioxidants (Basel) 11:723. PMID: 35453408 Open Access

Peugnet Victoriane,  Chwastyniak Maggy,  Mulder Paul,  Lancel Steve,  Bultot Laurent,  Fourny Natacha,  Renguet Edith,  Bugger Heiko,  Beseme Olivia,  Loyens Anne,  Heyse Wilfried,  Richard Vincent,  Amouyel Philippe,  Bertrand Luc,  Pinet Florence,  Dubois-Deruy Emilie (2022) Antioxidants (Basel)

Abstract: Heart failure, mostly associated with cardiac hypertrophy, is a major cause of illness and death. Oxidative stress causes accumulation of reactive oxygen species (ROS), leading to mitochondrial dysfunction, suggesting that mitochondria-targeted therapies could be effective in this context. The purpose of this work was to determine whether mitochondria-targeted therapies could improve cardiac hypertrophy induced by mitochondrial ROS. We used neonatal (NCMs) and adult (ACMs) rat cardiomyocytes hypertrophied by isoproterenol (Iso) to induce mitochondrial ROS. A decreased interaction between sirtuin 3 and superoxide dismutase 2 (SOD2) induced SOD2 acetylation on lysine 68 and inactivation, leading to mitochondrial oxidative stress and dysfunction and hypertrophy after 24 h of Iso treatment. To counteract these mechanisms, we evaluated the impact of the mitochondria-targeted antioxidant mitoquinone (MitoQ). MitoQ decreased mitochondrial ROS and hypertrophy in Iso-treated NCMs and ACMs but altered mitochondrial structure and function by decreasing mitochondrial respiration and mitophagy. The same decrease in mitophagy was found in human cardiomyocytes but not in fibroblasts, suggesting a cardiomyocyte-specific deleterious effect of MitoQ. Our data showed the importance of mitochondrial oxidative stress in the development of cardiomyocyte hypertrophy. We observed that targeting mitochondria by MitoQ in cardiomyocytes impaired the metabolism through defective mitophagy, leading to accumulation of deficient mitochondria. β€’ Keywords: Acetylation, Cardiac hypertrophy, Heart failure, Mitochondrial antioxidant, Mitochondrial dysfunction, Mitophagy, Oxidative stress, Superoxide dismutase 2 β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: FR Lille Lancel Steve

Labels: MiParea: Respiration  Pathology: Cardiovascular  Stress:Oxidative stress;RONS  Organism: Rat  Tissue;cell: Heart  Preparation: Intact cells 

Coupling state: LEAK, ROUTINE, ET  Pathway: ROX  HRR: Oxygraph-2k 


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