Mitochondria are dynamic organelles constantly undergoing fusion and fission. A concerted balance between the process of mitochondrial fusion and fission is required to maintain cellular health under different physiological conditions. Mutation and dysregulation of Drp1, the major driver of mitochondrial fission, has been associated with various neurological, oncological and cardiovascular disorders. Moreover, when subjected to pathological insults, mitochondria often undergo excessive fission, generating fragmented and dysfunctional mitochondria leading to cell death. Therefore, manipulating mitochondrial fission by targeting Drp1 has been an appealing therapeutic approach for cytoprotection. However, studies have been inconsistent. Studies employing Drp1 constructs representing alternate Drp1 isoforms, have demonstrated differing impacts of these isoforms on mitochondrial fission and cell death. Furthermore, there are distinct expression patterns of Drp1 isoforms in different tissues, suggesting idiosyncratic engagement in specific cellular functions. In this review, we will discuss these inherent variations among human Drp1 isoforms and how they could affect Drp1-mediated mitochondrial fission and cell death.

线粒体是不断发生融合和裂变的动态细胞器。线粒体融合和裂变过程之间需要协调一致的平衡，才能在不同的生理条件下维持细胞健康。Drp1是线粒体裂变的主要驱动力，其突变和失调与各种神经系统，肿瘤和心血管疾病有关。而且，当遭受病理性损伤时，线粒体经常经历过度裂变，产生破碎的和功能异常的线粒体，导致细胞死亡。因此，通过靶向Drp1操纵线粒体裂变已成为细胞保护的一种有吸引力的治疗方法。但是，研究一直不一致。使用代表其他Drp1同种型的Drp1构建体进行的研究，已证明这些同工型对线粒体裂变和细胞死亡的不同影响。此外，Drp1亚型在不同的组织中有不同的表达模式，表明特异参与特定的细胞功能。在这篇综述中，我们将讨论人类Drp1亚型之间的这些固有变异，以及它们如何影响Drp1介导的线粒体裂变和细胞死亡。