Mitochondria in the life and death of mechanosensory hair cells

Abstract

Hair cells are mechanosensory receptors found in the inner ear that mediate hearing and balance. In humans, damage and death of these cells is an underlying cause of hearing loss. Given the high prevalence of hearing loss, understanding the biology of these sensory cells continues to be an important endeavor to inform therapeutic strategies. The zebrafish has become a valuable model organism for advancing these efforts. In addition to hair cells of the inner ear, zebrafish also possess superficial hair cells of the lateral line sensory system, a sense devoted to detection of directional water flow. In combination with other advantages of the zebrafish model, the location of these hair cells has facilitated investigations of both normal hair cell function as well as mechanisms of hair cell death in vivo. In the following pages, I discuss the zebrafish as an auditory system model, highlighting structural and functional similarities between lateral line and cochlear hair cells, including selective susceptibility to environmental toxins. I then focus on a new investigation, relying on zebrafish to explore mitochondrial activity in lateral line hair cells. While this work is motivated by evidence demonstrating that mitochondria play a prominent role in hair cell damage and death, it begins to fill a gap in our understanding of how mitochondria function in response to normal cell activity. More specifically, I report on mitochondrial calcium flux and oxidation, finding that both are regulated by mechanotransduction. I also examine whether variation in mitochondrial activity reflects differences in hair cell vulnerability to the toxic drug neomycin. Overall, this study reveals a relationship between hair cell activity, mitochondrial activity, and susceptibility to damage.