Autophagy in Sensorineural Hearing Loss: Jekyll or Hyde?

Autophagy plays a key role in the development and homeostasis of the cochlear organ. Alterations in the autophagic pathways have been associated with damage to auditory cell types and hearing impairment caused by an array of factors like age, ototoxicity, exposure to high levels of noise, or genetic mutations. Cochlear damage frequently entails mitochondrial dysfunction, impaired mitophagy and the accumulation of high concentrations of free radicals. This review summarizes the observations made to date on the autophagic function in response to cochlear damage and the results of either activating or inhibiting these processes. The data demonstrate that autophagic activity is cell context-dependent and varies according to the cochlear cell type, the toxic agent, its levels and the length and timing of its administration; other factors that influence the autophagic response may be external to the auditory system or related to epigenetic changes or the expression of genetic variants. Modulation of the autophagic status has an effect on auditory cell loss and the progression to hearing impairment and this approach has thus become a promising avenue towards the protection of the hearing function. Nonetheless, this is no easy task and it will require the identification of reliable biomarkers to evaluate the dynamics of autophagic activity as well as the development of specific autophagy modulators that do not exert toxicity.