DRP1 haploinsufficiency attenuates cardiac ischemia/reperfusion injuries.
DRP1 haploinsufficiency attenuates cardiac ischemia/reperfusion injuries.
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DOI：
10.1371/journal.pone.0248554
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Mirebeau-Prunier D
中科院分区：
文献类型：
--
作者：
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
线粒体动力学可能是心肌缺血/再灌注损伤（IRI）的调节因子。我们先前报道了融合蛋白OPA 1部分缺陷的小鼠表现出更高的IRI。因此，我们研究了Dnm 1 l基因编码的分裂蛋白DRP 1的缺陷是否会影响Dnm 1 l +/-小鼠的IRI。在使用超声心动图、电子显微镜和血氧描记法对Dnm 1 l +/-小鼠心脏进行基线表征后，将3个月大的Dnm 1 l +/-和野生型（WT）小鼠暴露于心肌缺血/再灌注（I/R）。以缺血危险区（AAR）和坏死区（AN）为界，用AN/AAR表示梗死面积。在I/R之前和之后分析涉及线粒体动力学和自噬的蛋白质。在I/R后评估线粒体通透性转换孔（mPTP）开放敏感性。心脏重量和左心室功能在3、6和12月龄Dnm 1 l +/-小鼠中与WT相比无显著差异。Dnm 1 l +/-小鼠的心脏DRP 1蛋白表达水平比WT低60%，而线粒体面积和脂质降解显著高于WT，尽管线粒体呼吸参数和mPTP开放没有显著差异。I/R后，Dnm 1 l +/-小鼠的梗死面积显著小于WT（分别为34.6±3.1%和44.5± 3.3%; p<0.05），自噬标志物LC 3 II和P62仅在Dnm 1 l +/-小鼠中与基线条件相比显著增加。总而言之，数据表明，通过Dnm 1 l缺乏增加融合与针对IRI的保护相关，而在基础条件下心脏或线粒体功能没有改变。由于DRP 1单倍不足的这种保护机制增加了自噬标志物的表达。
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.
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影响因子：
29
作者：
Song M;Mihara K;Chen Y;Scorrano L;Dorn GW 2nd
通讯作者：
Dorn GW 2nd
影响因子：
11.1
作者：
Dorn GW 2nd
通讯作者：
Dorn GW 2nd
影响因子：
10.8
作者：
Chen, Le;Gong, Qizhi;Knowlton, Anne A.
通讯作者：
Knowlton, Anne A.
DOI：
10.1083/jcb.200903065
发表时间：
2009-09-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
Wakabayashi J;Zhang Z;Wakabayashi N;Tamura Y;Fukaya M;Kensler TW;Iijima M;Sesaki H
通讯作者：
Sesaki H
DOI：
10.1126/science.1219855
发表时间：
2012-08-31
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Youle RJ;van der Bliek AM
通讯作者：
van der Bliek AM