线粒体融合蛋白2在心血管疾病中的研究现状

线粒体是一个处于不断地融合与分裂过程中的动态细胞器。线粒体融合蛋白2(Mfn2)作为广泛分布于线粒体外膜和线粒体结合内质网膜上具有多重功能的蛋白,参与维持正常细胞功能。除了参与线粒体融合外,Mfn2还能够调节线粒体代谢、促进损伤线粒体的自噬、增强线粒体与内质网交流、维持内质网功能及通过调控线粒体外膜通透性和渗透性钙转运孔道的启闭参与细胞死亡过程等。另外,Mfn2基因还可通过调控Ras-Raf-ERK/MAPK和Ras-PI3K-Akt信号通路分别参与调控血管平滑肌细胞的增殖和凋亡过程。Mfn2的这一系列重要的生物学功能有助于其参与高血压、肺动脉高压、动脉粥样硬化、急性缺血/再灌损伤、扩张性心肌病、心肌肥大、心衰和肥胖糖尿病等多种心血管疾病的发生发展过程。研究Mfn2与心血管疾病的相关性也许能为临床提供一个心血管疾病潜在治疗的靶点。因此,本文将综述Mfn2在心血管疾病相关研究中的现状。

Mitofusin-2 in cardiac diseases

Mitochondria are highly dynamic organelles with constant fusion and fission. Mitofusin-2( Mfn2) is widely distributed on the outer membrane of mitochondria and mitochondria-associated endoplasmic reticulum membrane( MAM) with multiple functions to sustain normal cell function. In addition to promoting mitochondrial fusion,Mfn2 also participates in injured mitochondria mitophagy,tethers endoplasmic reticulum( ER) to mitochondria,sustains ER structure and functions and plays critical roles in several cell death pathways( including apoptosis and necrotic cell death) by mediating mitochondrial outer membrane permeabilization and facilitating opening of the mitochondrial permeability pore( m PTP)during death. Moreover,Mfn2 gene regulates vascular smooth muscle cell( VSMC) proliferation via Ras-Raf-ERK / MAPK and Ras-PI3K-Akt pathways. Mfn2 is associated with cardiac diseases including hypertension,pulmonary artery hypertension,atherosclerosis,dilated cardiomyopathy,acute ischemic reperfusion injury,cardiac hypertrophy,heart failure and major metabolic disturbance such as diabetes and obesity. Exploration of the relationships between Mfn2 and cardiac diseases may provide therapeutic potentials for cardiac diseases.