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Updated: Aug 14, 2026
Modified Experimental Conditions for Noise-Induced Hearing Loss in Mice and Assessment of Hearing Function and Outer Hair Cell Damage
Published on: February 10, 2023
AIF and endoG translocation in noise exposure induced hair cell death
Weiju Han1, Xiaorui Shi, Alfred L Nuttall
1Oregon Hearing Research Center, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, NRC04, Portland, OR 972390-3098, USA.
Abstract:
Activation of caspases is a key element in the apoptotic process. However, mitochondria also play an important role via the release of proapoptotic proteins. This study investigated the roles of mitochondria-related apoptosis inducing factor (AIF) and endonuclease G (endoG), mitochondrion-specific nucleases, as well as caspase-3, an important mediator of apoptosis, in noise exposure induced hair cell death. Guinea pigs were exposed for 4h/day to broadband noise at 122 dB SPL for 2 days. After the noise exposure, the cochleae were examined for the activity of caspase-3 with carboxyfluorescein-labeled fluoromethyl ketone (FMK)-peptide inhibitors. The cochleae were further examined for AIF and endoG translocation from the mitochondria by immunohistochemistry. Noise exposure triggered activation of caspase-3 in apoptotic hair cells. In the normal organ of Corti, AIF and endoG were co-localized to the mitochondria. After noise exposure, AIF translocated into the nuclei of apoptotic and necrotic hair cells. The translocation of endoG from mitochondria into the nucleus was also found in apoptotic OHCs. These findings indicate that mitochondria-released proapoptotic proteins, AIF and endoG, are important factors in a noise-induced hair cell death pathway.
Insights
Mitochondria-released proteins, apoptosis-inducing factor (AIF) and endonuclease G (endoG), play key roles in noise-induced hair cell death. Noise exposure triggers caspase-3 activation and translocation of AIF and endoG, leading to apoptosis.
Area of Science:
- Otoacoustic emissions
- Auditory neuroscience
- Cellular biology
Background:
- Apoptosis, or programmed cell death, is crucial for cellular homeostasis.
- Mitochondria play a significant role in apoptosis through the release of proapoptotic proteins.
- Noise-induced hearing loss is a common form of sensorineural hearing loss.
Purpose of the Study:
- To investigate the roles of apoptosis-inducing factor (AIF), endonuclease G (endoG), and caspase-3 in noise-induced hair cell death.
- To determine if AIF and endoG translocate from mitochondria during noise exposure.
- To elucidate the mechanisms of hair cell death following acoustic trauma.
Main Methods:
- Guinea pigs were exposed to broadband noise (122 dB SPL) for 4 hours/day over 2 days.
- Caspase-3 activity was assessed using carboxyfluorescein-labeled fluoromethyl ketone (FMK)-peptide inhibitors.
- Immunohistochemistry was employed to examine the translocation of AIF and endoG from mitochondria.
Main Results:
- Noise exposure activated caspase-3 in hair cells undergoing apoptosis.
- AIF and endoG were localized to mitochondria in the normal organ of Corti.
- Following noise exposure, AIF translocated to the nuclei of apoptotic and necrotic hair cells, and endoG translocated to the nucleus in apoptotic outer hair cells (OHCs).
Conclusions:
- Mitochondria-released proteins, AIF and endoG, are critical mediators in the pathway of noise-induced hair cell death.
- The translocation of these proteins from mitochondria contributes to the apoptotic process in hair cells.
- Understanding these mechanisms may lead to novel therapeutic strategies for preventing noise-induced hearing loss.
