Functionally and morphologically damaged mitochondria observed in auditory cells under senescence-inducing stress

Area of Science:

• Cell Biology
• Otolaryngology
• Mitochondrial Biology

Background:

• Cellular senescence contributes to age-related hearing loss.
• Mitochondrial dysfunction is implicated in various senescence processes.
• Auditory cells are susceptible to oxidative stress.

Purpose of the Study:

• To investigate the role of mitochondrial function in hydrogen peroxide (H₂O₂)-induced premature senescence in auditory cells.
• To determine the early molecular events leading to senescence in these cells.

Main Methods:

• Induction of premature senescence in House Ear Institute-Organ of Corti 1 auditory cells using short-term H₂O₂ exposure.
• Transmission electron microscopy (TEM) for ultrastructural analysis of mitochondria.
• Analysis of mitochondrial network parameters (branching, junctioning).
• Assessment of mitochondrial membrane potential and respiratory capacity.
• Evaluation of ATP production rates and response to uncoupling reagents.

Main Results:

• H₂O₂ exposure caused premature senescence, characterized by damaged mitochondria and autophagosomes.
• Mitochondrial network analysis revealed decreased branching and junctioning, indicating fragmentation.
• A dose-dependent decrease in mitochondrial membrane potential was observed.
• Mitochondrial respiratory capacity was impaired, while baseline ATP production remained unaffected.
• Auditory cells showed increased vulnerability of mitochondrial membrane potential to uncoupling agents.

Conclusions:

• Mitochondrial dysfunction, specifically reduced oxygen consumption rate, is an early event in H₂O₂-induced auditory cell senescence.
• This dysfunction leads to imbalanced mitochondrial fusion/fission dynamics and mitochondrial network collapse.
• Targeting mitochondrial health may be a strategy to mitigate premature auditory cell senescence.