Sestrin 2 Deficiency Exacerbates Noise-Induced Cochlear Injury Through Inhibiting ULK1/Parkin-Mediated Mitophagy.

Aims: Noise damage to auditory hair cells is associated with oxidative stress and mitochondrial dysfunction. This study aimed to investigate the possible effect of sestrin 2 (SESN2), an endogenous antioxidant protein, on noise-induced hearing loss (NIHL) and the underlying mechanisms. Results: We identified SESN2 as a protective factor against oxidative stress in NIHL through activation of Parkin-mediated mitophagy. Consistently, SESN2 expression was increased and mitophagy was induced during the early stage after a temporary threshold shift due to noise exposure or hydrogen peroxide(H2O2) stimulation; conversely, SESN2 deficiency blocked mitophagy and exacerbated acoustic trauma. Mechanistically, SESN2 interacted with Unc-51-like protein kinase 1(ULK1), promoting ULK1 protein-level stabilization by interfering with its proteasomal degradation. This stabilization is essential for mitophagy initiation, since restoring ULK1 expression in SESN2-silenced cells rescued mitophagy defects. Innovation and Conclusion: Our results provide novel insights regarding SESN2 as a therapeutic target against noise-induced cochlear injury, possibly through improved mitophagy. Antioxid. Redox Signal. 38, 115-136.

Olfactory-auditory sensory integration in the lateral entorhinal cortex.

Multisensory integration plays an important role in animal cognition. Although many studies have focused on visual-auditory integration, studies on olfactory-auditory integration are rare. Here, we investigated neural activity patterns and odor decoding in the lateral entorhinal cortex (LEC) under uni-sensory and multisensory stimuli in awake, head-fixed mice. Using specific retrograde tracing, we verified that the LEC receives direct inputs from the primary auditory cortex (AC) and the medial geniculate body (MGB). Strikingly, we found that mitral/tufted cells (M/Ts) in the olfactory bulb (OB) and neurons in the LEC respond to both olfactory and auditory stimuli. Sound decreased the neural responses evoked by odors in both the OB and LEC, for both excitatory and inhibitory responses. Interestingly, significant changes in odor decoding performance and modulation of odor-evoked local field potentials (LFPs) were observed only in the LEC. These data indicate that the LEC is a critical center for olfactory-auditory multisensory integration, with direct projections from both olfactory and auditory centers.