title: Mitochondrial fission - a drug target for cytoprotection or cytodestruction?
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.
authors.affiliation: 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.
authors.forename: Ayeshah A
authors.initials: AA
authors.lastname: Rosdah
authors.affiliation: ACRF Rational Drug Discovery Centre St Vincent's Institute of Medical Research Victoria Australia.
authors.forename: Jessica
authors.initials: J
authors.lastname: K Holien
authors.affiliation: Department of Physiology University of Melbourne Victoria Australia.
authors.forename: Lea M D
authors.initials: LM
authors.lastname: Delbridge
authors.affiliation: O'Brien Institute Department St Vincent's Institute of Medical Research Victoria Australia; Centre for Eye Research Australia Royal Victorian Eye and Ear Hospital Victoria Australia; Department of Surgery University of Melbourne Victoria Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dusting
authors.affiliation: O'Brien Institute Department St Vincent's Institute of Medical Research Victoria Australia; Department of Surgery University of Melbourne Victoria Australia.
authors.forename: Shiang Y
authors.initials: SY
authors.lastname: Lim
keywords: Cell death; Mdivi‐1; mitochondrial fission; mitochondrial fusion