Discovery and characterization of selective small molecule inhibitors of the mammalian mitochondrial division dynamin, DRP1.

ABSTRACT: Balanced rates of mitochondrial division and fusion are required to maintain mitochondrial function, as well as cellular and organismal homeostasis. In mammals, the cellular machines that mediate these processes are dynamin-related GTPases; the cytosolic DRP1 mediates division, while the outer membrane MFN1/2 and inner membrane OPA1 mediate fusion. Unbalanced mitochondrial dynamics are linked to varied pathologies, including cell death and neurodegeneration, raising the possibility that small molecules that target the division and fusion machines to restore balance may have therapeutic potential. Here we describe the discovery of novel small molecules that directly and selectively inhibit assembly-stimulated GTPase activity of the division dynamin, DRP1. In addition, these small molecules

SUBMITTER: Mallat A 

PROVIDER: S-EPMC6626631 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature