Development of cancer cell death inducer via interfering MFF-VDAC interaction

Abstract

Mitochondria regulate energy metabolism, biosynthesis, cell death, redox homeostasis and signaling pathway and dysregulated mitochondria abundantly observed in cancer. Therefore, researchers tried to targeting mitochondria for killing cancer. The mitochondrial fission factor (MFF) and voltage-dependent anion channel (VDAC) form a complex which of interruption activates mitochondrial outer membrane permeability (MOMP) and induces cell death. MFF peptide, synthetic MFF sequence peptide that competitively inhibit MFF and VDAC interaction, treatment leads to mitochondrial cell death in cancer but not in normal. However, due to poor stability of peptide in vivo, it is needed to develop new substance that inducing cell death via interfering of MFF-VDAC interaction like MFF peptide. We developed chemical screening system to seek chemical interfering MFF-VDAC interaction using nanobit protein-protein interaction assay system which is structural complementation reporter system. The chemical identified from this assay system could be a new anti-cancer drug that is targeting mitochondria to induce cancer cell death.