The role of mitochondrial oxidative stress in hearing loss

Abstract

Hearing loss is the most common form of sensory impairment in humans, affecting 5.3% worldwide population. Although approximately 1 in 500 children are born with impaired hearing, sudden or progressive forms of hearing loss can manifest at any age. Hearing impairment following cochlear damage due to noise trauma, ototoxicity or age-related cochlear degeneration was linked to a common pathogenesis involving the formation of reactive oxygen species (ROS). This review summarizes the current data suggesting a role of mitochondrial ROS overproduction in hearing loss and the molecular mechanism involved in hair cell apoptosis responsible of this disorder. Because increasing number of studies demonstrated that antioxidants and free radical scavengers may serve as effective compounds to block the activation of cochlear hair cell death, targeting members of antioxidant pathways and in the breakdown of superoxide anions and hydrogen peroxidase, could be feasible options for the treatment of several types of hearing loss.Correspondence to: Sergio Gonzalez-Gonzalez, CILcare, 2214, Boulevard de la Lironde. Parc Scientifique Agropolis, Montpellier, France, E-mail: sergio. gonzalez@cilcare.com Cochlea and hair cellsThe mammalian cochlea is the sensory organ capable of perceiving sound over a range of pressure, and discriminating both infrasonic and ultrasonic frequencies in different species. The organ of Corti is located in the cochlea of the inner ear and is responsible for the detection of sound. This organ harbours the auditory sensory epithelium, which, in humans, contains approximately 16,000 hair cells that are patterned into three rows of outer hair cells (OHCs) and one row of inner hair cells (IHCs) [1,2]. Each hair cell contains, at its apical surface, a mechanically sensitive organelle that consists of rows of actin-filled stereocilia that increasein height. An extracellular matrix, the tectorial membrane, covers the apical surface of the organ of Corti and is attached to the hair bundles of OHCs. The cell bodies of hair cells form specialized adhesive contacts with supporting cells that adhere at their basolateral surfaces to the basilar membrane, an extracellular matrix assembly with a different molecular composition from the tectorial membrane [3,4].Hearing is initiated when sound waves that reach the outer ear travel through the ear canal to the tympanic membrane. Then, the sound energy is transferred, via the bony ossicles of the middle ear, to the oval window at the base of the fluid-filled cochlea. The motions of the oval window are converted into fluid pressure waves that induce vibrations in the basilar membrane. Then, the vibrations are transferred onto the hair cells, leading to the deflection of the hair cell stereocilia [5]. This deflection causes stretch-sensitive ion channels to open. These are non-selectively permeable to cations and are located at the base of the tip links, with 1 or 2 channels per tip link. Stereocilia bathe in endolymph, which is rich in potassium and characterized by an ...

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