MFI8 (Mitochondrial Fusion Inhibitor 8) is a small molecule inhibitor of mitochondrial fusion via mitofusins (MFN1 and MFN2), concentration-responsively decreases mitochondrial aspect ratio (Mito AR) in MEFs with EC50 of 4.8 uM.
MFI8 shows a comparable concentration-dependent reduction of the mitochondrial aspect ratio to that of 398-418 Gly peptide.
MFI8 inhibits mitochondrial fusion in a MFN1/2 dependent manner, binds to the HR2 domain of MFN2 with KD of 7.6 uM in microscale thermophoresis (MST) assay.
MFI8 induces mitochondrial outer membrane permeabilization (MOMP) and subsequent activation of caspases 3/7, induces DNA damage in U2OS cells.
MFI8 reduced respiration and mitochondrial ATP production in WT but not in Mfn1/Mfn2 DKO MEFs, does not alter the ratio of state III/state II respiration of isolated mitochondria.
MFI8 induces minority MOMP and cytochrome c release leading to caspase 3/7 activation, sensitize cells to apoptotic cell death in combination with SMAC-mimetic BV6.