Ferritin light-chain contributes to hair cells function and survival

Iron is essential for cellular function, as it is required for oxygen transport and mitochondria oxidative respiration. However, uncoordinated regulation of intracellular iron can produce reactive oxygen species, calling for a tight homeostasis. Here, we examine the role of the iron-binding protein, ferritin, known to store intracellular iron, in the cochlea. Genetic ablation of the ferritin light-chain (Ftl1) in mouse leads to two different phenotypes. Nearly 20% of the homozygous mice have moderate to profound hearing loss (Ftl1-/- with High-Threshold, HT), with the other fraction of mice unaffected, i.e., with normal auditory threshold (Ftl1-/- with Low-Threshold, LT). In the fraction of Ftl1-/- HT mice, the outer hair cells, which amplify incoming sound-stimulation, undergo a massive degeneration and the inner hair cells, which converts the mechanical pressure into exocytosis of glutamate, harbor splayed hair bundles. In addition, patch-clamp recordings demonstrated the alteration of calcium current in the IHCs from Ftl1-/- HT mice. Finally, the Ftl1-/- LT mice were found to be more vulnerable to acoustic exposure, suggesting that the difference between the two phenotypes may partly stem from noxious environment. Taken together, our results suggest that ferritin light-chain is a contributing factor to the hair cell function and survival. *Chloé P. Petit & Sahia Mahaman Bachir Dodo contributed equally to this work.