Targeting Mitochondrial Dynamics during Lower-Limb Ischemia Reperfusion in Young and Old Mice: Effect of Mitochondrial Fission Inhibitor-1 (mDivi-1).

Stephanie Paradis (1) , Anne-Laure Charles , Margherita Giannini (1) , Alain Meyer (1) , Anne Lejay (1) , Samy Talha (1) , Gilles Laverny (2) , Anne Charloux (1) , Bernard Geny (1)

1 MSP - Mitochondrie, Stress oxydant et Protection musculaire
2 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire

Peripheral arterial disease (PAD) strikes more than 200 million people worldwide and has a severe prognosis by potentially leading to limb amputation and/or death, particularly in older patients. Skeletal muscle mitochondrial dysfunctions and oxidative stress play major roles in this disease in relation with ischemia-reperfusion (IR) cycles. Mitochondrial dynamics through impairment of fission-fusion balance may contribute to skeletal muscle pathophysiology, but no data were reported in the setting of lower-limb IR despite the need for new therapeutic options. We, therefore, investigated the potential protective effect of mitochondrial division inhibitor-1 (mDivi-1; 50 mg/kg) in young (23 weeks) and old (83 weeks) mice submitted to two-hour ischemia followed by two-hour reperfusion on systemic lactate, muscle mitochondrial respiration and calcium retention capacity, and on transcripts specific for oxidative stress and mitochondrial dynamics. At the systemic levels, an IR-related increase in circulating lactate was still major despite mDivi-1 use (+305.9%

Mots clés: drug therapy

Domaines: Biochimie, Biologie Moléculaire

Stephanie Paradis, Anne-Laure Charles, Margherita Giannini, Alain Meyer, Anne Lejay, et al.. Targeting Mitochondrial Dynamics during Lower-Limb Ischemia Reperfusion in Young and Old Mice: Effect of Mitochondrial Fission Inhibitor-1 (mDivi-1).. International Journal of Molecular Sciences, 2024, 25 (7), ⟨10.3390/ijms25074025⟩. ⟨hal-04551969⟩