AMPK activation by AICAR induces mitochondrial biogenesis in the inner ear

Abstract

RationaleThe importance of mitochondrial biogenesis to auditory hair cell physiology or that of the non‐sensory cells in the cochlea is poorly understood. Activation of 5′ AMP activated protein kinase (AMPK) upregulates peroxisome proliferator–activated receptor‐γ coactivator‐1α (PGC‐1α) which, in turn, increases the levels of factors involved in mitochondrial biogenesis and respiration. At the same time, AMPK activation can increase antioxidant expression and reduce reactive oxygen species generation.ObjectiveTo determine whether the AMPK activator 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside (AICAR) can induce mitochondrial biogenesis in the inner ear and protect against noise induced hearing loss.Methods and ResultsAICAR treatment in mice led to higher levels of phosphorylated AMPKα in the cochlea by immunoblot and immunohistochemistry (IHC) analysis. Quantitative real‐time PCR revealed increased PGC‐1α mRNA levels. Extended AICAR treatment increased mitochondrial fission protein 1 and superoxide dismutase 2 protein levels. Auditory brainstem response analysis demonstrated that AICAR treatment accelerated recovery from acoustic trauma.ConclusionThese results demonstrate that mitochondria in the inner ear have the capacity to be dynamically regulated with increasing energy demands.Supported by grants 5R01DC000105 (ALN), 1R01DC010844 (XS), and P30DC005983.