P259 is a Drp1-Mff inhibitor that selectively impedes the interaction between Drp1 and Mff, thereby differentiating physiological fission from pathological fission. It leads to mitochondrial elongation and impairs mitochondrial function and motility. P259 reduces ATP levels in the brain, alters mitochondrial structure, induces behavioral defects in wild-type mice, and shortens the lifespan of Huntington's disease (HD) model mice.