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线粒体裂变:细胞保护还是细胞破坏的药物靶点?

Mitochondrial fission - a drug target for cytoprotection or cytodestruction?

机构信息

O'Brien Institute Department St Vincent's Institute of Medical Research Victoria Australia; Department of Physiology University of Melbourne Victoria Australia; Faculty of Medicine Sriwijaya University Palembang Indonesia.

ACRF Rational Drug Discovery Centre St Vincent's Institute of Medical Research Victoria Australia.

出版信息

Pharmacol Res Perspect. 2016 Apr 21;4(3):e00235. doi: 10.1002/prp2.235. eCollection 2016 Jun.

Abstract

Mitochondria are morphologically dynamic organelles constantly undergoing processes of fission and fusion that maintain integrity and bioenergetics of the organelle: these processes are vital for cell survival. Disruption in the balance of mitochondrial fusion and fission is thought to play a role in several pathological conditions including ischemic heart disease. Proteins involved in regulating the processes of mitochondrial fusion and fission are therefore potential targets for pharmacological therapies. Mdivi-1 is a small molecule inhibitor of the mitochondrial fission protein Drp1. Inhibiting mitochondrial fission with Mdivi-1 has proven cytoprotective benefits in several cell types involved in a wide array of cardiovascular injury models. On the other hand, Mdivi-1 can also exert antiproliferative and cytotoxic effects, particularly in hyperproliferative cells. In this review, we discuss these divergent effects of Mdivi-1 on cell survival, as well as the potential and limitations of Mdivi-1 as a therapeutic agent.

摘要

线粒体是形态上动态的细胞器,不断经历分裂和融合的过程,以维持细胞器的完整性和生物能量学:这些过程对细胞存活至关重要。线粒体融合和分裂平衡的破坏被认为在几种病理状况中起作用,包括缺血性心脏病。因此,参与调节线粒体融合和分裂过程的蛋白质是药理学治疗的潜在靶点。Mdivi-1 是一种线粒体裂变蛋白 Drp1 的小分子抑制剂。用 Mdivi-1 抑制线粒体裂变已被证明在几种涉及广泛心血管损伤模型的细胞类型中具有细胞保护作用。另一方面,Mdivi-1 也可以发挥抗增殖和细胞毒性作用,特别是在过度增殖的细胞中。在这篇综述中,我们讨论了 Mdivi-1 对细胞存活的这些不同影响,以及 Mdivi-1 作为治疗剂的潜力和局限性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae8b/4876145/11bf403a013e/PRP2-4-e00235-g001.jpg

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