Project Summary Mitochondrial dysfunction has long been recognized as an underlying mechanism of noise-induced loss of hearing sensitivity (NIHL). However, the initiating processes that lead to this dysfunction is poorly understood. This proposal is founded upon new and important findings involving changes in mitochondrial dynamics in outer hair cells after loud sound exposure. Mitochondria are highly dynamic organelles that constantly undergo fission and fusion to adapt to changes in the cellular environment, and it is becoming increasingly clear that mitochondrial morphology is directly related to mitochondrial function and, therefore, the health and survival of the cell. The studies proposed here will examine a potential integrin signaling pathway for induction of mitochondrial fission activity. Specifically, we will investigate the role of FAK as a mediator of noise-induced overstimulation of OHCs leading to cell death and loss of hearing sensitivity.