Bouche 2021 PLoS One
|Bouche L, Kamel R, Tamareille S, Garcia G, Villedieu C, Pillot B, Gueguen N, Chehaitly A, Chao de la Barca JM, Beaumont J, Baetz D, Ovize M, Sesaki H, Henrion D, Reynier P, Lenaers G, Prunier F, Mirebeau-Prunier D (2021) DRP1 haploinsufficiency attenuates cardiac ischemia/reperfusion injuries. PLoS One 16:0248554.|
Bouche Laura, Kamel Rima, Tamareille Sophie, Garcia Gabriel, Villedieu Camille, Pillot Bruno, Gueguen Naig, Chehaitly Ahmad, Chao de la Barca Juan Manuel, Beaumont Justine, Baetz Delphine, Ovize Michel, Sesaki Hiromi, Henrion Daniel, Reynier Pascal, Lenaers Guy, Prunier Fabrice, Mirebeau-Prunier Delphine (2021) PLoS One
Abstract: Mitochondrial dynamics is a possible modulator of myocardial ischemia/reperfusion injuries (IRI). We previously reported that mice partially deficient in the fusion protein OPA1 exhibited higher IRI. Therefore, we investigated whether deficiency in the fission protein DRP1 encoded by Dnm1l gene would affect IRI in Dnm1l+/- mouse. After baseline characterization of the Dnm1l+/- mice heart, using echocardiography, electron microscopy, and oxygraphy, 3-month-old Dnm1l+/- and wild type (WT) mice were exposed to myocardial ischemia/reperfusion (I/R). The ischemic area-at-risk (AAR) and area of necrosis (AN) were delimited, and the infarct size was expressed by AN/AAR. Proteins involved in mitochondrial dynamics and autophagy were analyzed before and after I/R. Mitochondrial permeability transition pore (mPTP) opening sensitivity was assessed after I/R. Heart weight and left ventricular function were not significantly different in 3-, 6- and 12-month-old Dnm1l+/- mice than in WT. The cardiac DRP1 protein expression levels were 60% lower, whereas mitochondrial area and lipid degradation were significantly higher in Dnm1l+/- mice than in WT, though mitochondrial respiratory parameters and mPTP opening did not significantly differ. Following I/R, the infarct size was significantly smaller in Dnm1l+/- mice than in WT (34.6±3.1% vs. 44.5±3.3%, respectively; p<0.05) and the autophagic markers, LC3 II and P62 were significantly increased compared to baseline condition in Dnm1l+/- mice only. Altogether, data indicates that increasing fusion by means of Dnm1l deficiency was associated with protection against IRI, without alteration in cardiac or mitochondrial functions at basal conditions. This protection mechanism due to DRP1 haploinsufficiency increases the expression of autophagic markers.
Labels: MiParea: Respiration, mt-Structure;fission;fusion, Genetic knockout;overexpression Pathology: Cardiovascular Stress:Ischemia-reperfusion Organism: Mouse Tissue;cell: Heart Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS, ET Pathway: F, N, S, CIV, NS, ROX HRR: Oxygraph-2k