Dynamin-1-like protein-Mitochondrial fission 1 protein interface (Drp1-Fis1 interface)

The Dynamin-1-like protein (Drp1) and Mitochondrial fission 1 protein (Fis1) interface is a critical regulatory site for mitochondrial fission, involving the recruitment of the cytosolic GTPase Drp1 to the mitochondrial outer membrane by the adapter protein Fis1 [PMID: 23550057]. Under physiological conditions, this interaction contributes to the balanced cycle of mitochondrial fusion and fission necessary for organelle health; however, its overactivation is a hallmark of several pathological states [PMID: 21900442]. Excessive Drp1-Fis1 mediated fission leads to mitochondrial fragmentation, increased reactive oxygen species production, and the induction of apoptotic pathways, which are central to the progression of neurodegenerative diseases like Parkinson's and Alzheimer's, as well as acute injuries like myocardial infarction [PMID: 27113476, 30639464]. Therapeutic targeting of this specific interface aims to block the pathological recruitment of Drp1 without disrupting its essential basal functions or its interactions with other mitochondrial adapters like Mff [PMID: 23550057]. The most prominent pharmacological tool for this target is the selective peptide inhibitor P110, which has demonstrated neuroprotective and cardioprotective efficacy in various preclinical models by preserving mitochondrial integrity [PMID: 29461516]. Consequently, the Drp1-Fis1 interface represents a high-value target for drug development in conditions characterized by mitochondrial dysfunction.

Other names

Drp1-Fis1 interactionDNM1L-FIS1 complexMitochondrial fission protein 1-Dynamin-related protein 1 interfaceDrp1-Fis1 protein-protein interaction

Inhibition of the recruitment of Dynamin-1-like protein (Drp1) to the mitochondrial outer membrane by Mitochondrial fission 1 protein (Fis1), thereby selectively reducing pathological mitochondrial fragmentation.