Mitochondrial fusion and division proteins function via self assembly to regulate membrane dynamics during various cellular events. For example, the self assembly of dynamin-1, a mitochondrial protein that facilitates endocytosis, with a dynamin related-GTPase (Dnm1 (yeast)/Drp1(mammals)), a mitochondrial protein that functions during mitochondrial division, is thought to regulate apoptosis. Mdivi 1 is a quinazolinone derivative that selectively inhibits mitochondrial division by blocking dynamin GTPase activity in yeast (IC50 = 1-10 μM) and mammalian cells (IC50 = ~50 μM). It has been shown to prevent apoptosis by inhibiting mitochondrial outer membrane permeabilization in vivo and to block Bid-activated Bax/Bak-dependent cytochrome c release from mitochondria in vitro. It has been used to maintain mitochondrial integrity and to prevent cell death in models of pathological conditions including cancer, heart failure, and ischemia and reperfusion injuries.
