Figure 12. Overview of the regulation of redox homeostasis and Tsc/mTORC1 signaling in cochlear hair cells.

In response to ROS, the Tsc complex localized to the peroxisome to regulate mTORC1 signaling and autophagy in hair cells. Deletion of Tsc1 caused hyperactivation of mTORC1 signaling, inducing oxidative damage and autophagy breakdown, which further resulted in hair cell damage and caused hearing deficits. Conversely, deletion of the mTORC1 component Raptor inactivated mTORC1 signaling, thus promoting the survival of hair cells and delaying the process of ARHL in C57BL/6J mice. Injection of rapamycin, which is an mTORC1 inhibitor, also protected cells against oxidative stress, thus preventing the development of ARHL.