Exogenous humanin and MOTS-c function as protective agents against gentamicin-induced hair cell damage

Loss of hair cells can lead to irreversible sensorineural hearing loss. Therefore, hair cell preservation is critical for hearing. Mitochondrial derived peptides (MDPs) are bioactive peptides and prominent members of this family are humanin (HN) and the mitochondrial-open-reading frame of the twelve S c (MOTS-c). The protective roles of HN and MOTS-c in age-related diseases and in various tissues exposed to cellular stresses have been demonstrated. The involvement of MDPs in the inner ear remains to be investigated. Therefore, we determined the expression of rattin, the homolog of humanin, in inner ear tissues. Then, we found that HN and MOTS-c showed a significant protective effect on hair cells in organ of Corti explants exposed to gentamicin. Treatment with HN decreased gentamicin-induced phosphorylation of AKT, whereas treatment with MOTS-c increased phosphorylation of AMPKα in explants. Our data indicate that MDPs exert a protective function in gentamicin-induced hair cell damage. Therefore, MDPs may contribute to design new preventive strategies against hearing loss. [Display omitted] •Rattin is endogenously expressed in cochlear cells.•Exogenous humanin and MOTS-c protect hair cells against gentamicin toxicity.•Exogenous humanin prevents gentamicin-induced AKT activation in cochlear cells.•Exogenous MOTS-c increases AMPKα-phosphorylation in cochlear cells.