Figure 1. Proposed model for the pathogenesis of hearing impairment in Huntington's disease (HD). Mitochondrial creatine kinase (CKMT1) phosphorylates creatine (Cr) and converts it to phosphocreatine (PCr), while brain-type creatine kinase (CKB) regenerates ATP from PCr. Because the stereocilia contain no mitochondria, the PCr-CK system plays a critical role in hair bundles of hair cells. Expression of mutant Huntingtin (Htt) in hair cells impairs the functioning of mitochondria, suppresses the expression of CKB, and elevates levels of reactive oxygen species (ROS). Creatine supplementation in HD mice ameliorates the reduced expression of CKB via an unidentified pathway, and subsequently improves the hearing impairment in HD mice.