Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Medicine Lab, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.12023. Epub 2021 Mar 24.
Platelet mitophagy is a major pathway involved in the clearance of injured mitochondria during hemostasis and thrombosis. Prohibitin 2 (PHB2) has recently emerged as an inner mitochondrial membrane receptor involved in mitophagy. However, the mechanisms underlying PHB2‑mediated platelet mitophagy and activation are not completely understood. PHB2 is a highly conserved inner mitochondrial membrane protein that regulates mitochondrial assembly and function due to its unique localization on the mitochondrial membrane. The present study aimed to investigate the role and mechanism underlying PHB2 in platelet mitophagy and activation. Phorbol‑12‑myristate‑13‑acetate (PMA) was used to induce MEG‑01 cells maturation and differentiate into platelets following PHB2 knockdown. Cell Counting Kit‑8 assays were performed to examine platelet viability. Flow cytometry was performed to assess platelet mitochondrial membrane potential. RT‑qPCR and western blotting were conducted to measure mRNA and protein expression levels, respectively. Subsequently, platelets were exposed to CCCP and the role of PHB2 was assessed. The results of the present study identified a crucial role for PHB2 in platelet mitophagy and activation, suggesting that PHB2‑mediated regulation of mitophagy may serve as a novel strategy for downregulating the expression of platelet activation genes. Although further research into mitophagy is required, the present study suggested that PHB2 may serve as a novel therapeutic target for thrombosis‑related diseases due to its unique localization on the mitochondrial membrane.
血小板线粒体自噬是止血和血栓形成过程中清除损伤线粒体的主要途径。抑制素 2（PHB2）最近作为一种参与线粒体自噬的线粒体内膜受体而出现。然而，PHB2 介导的血小板线粒体自噬和激活的机制尚不完全清楚。PHB2 是一种高度保守的线粒体内膜蛋白，由于其独特的定位于线粒体膜上，调节线粒体的组装和功能。本研究旨在探讨 PHB2 在血小板线粒体自噬和激活中的作用和机制。佛波醇 12-肉豆蔻酸 13-乙酸酯（PMA）用于诱导 MEG-01 细胞成熟，并在 PHB2 敲低后分化为血小板。细胞计数试剂盒-8 测定用于检测血小板活力。流式细胞术用于评估血小板线粒体膜电位。RT-qPCR 和 Western blot 用于分别测量 mRNA 和蛋白表达水平。随后，用 CCCP 处理血小板，并评估 PHB2 的作用。本研究结果确定了 PHB2 在血小板线粒体自噬和激活中的关键作用，表明 PHB2 介导的线粒体自噬调节可能成为下调血小板激活基因表达的新策略。尽管需要进一步研究线粒体自噬，但本研究表明，由于 PHB2 独特的定位于线粒体膜上，它可能成为与血栓形成相关疾病的新的治疗靶点。
