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

Abstract

We aimed at determining the mitochondrial function in premature senescence model of auditory cells. Short exposure to H₂O₂ (1 h, 0.1 mM) induced premature cellular senescence in House Ear Institute-Organ of Corti 1 auditory cells. The transmission electron microscopy analysis revealed that damaged mitochondria and autophagosomes containing dense organelles appeared in the auditory cells after short exposure to H₂O₂. The branch and junction parameters of the skeletonized image of the mitochondria were found to decrease significantly in H₂O₂-treated cells. A branched reticulum of tubules was poorly formed, featuring coexistence of numerous tiny clusters along with few relatively large entities in the H₂O₂-treated cells. In terms of bioenergetics, H₂O₂-treatment led to the dose-dependent decrease in mitochondrial membrane potential in the auditory cells. The fragmented mitochondria (fusion < fission) were in a low potential. In addition, the potential of hyperfused mitochondria (fusion > fission) was slightly lower than the control cells. The short-time exposure of live auditory cells to H₂O₂ damaged the mitochondrial respiratory capacity without any effect on the baseline ATP production rates. The vulnerability of the mitochondrial membrane potential to the uncoupling reagent was increased after H₂O₂ treatment. Our findings indicated that the mitochondrial dysfunction due to the decline in the O₂ consumption rate should be the first event of premature senescence process in the auditory cells, resulting in the imbalance of mitochondrial fusion/fission and the collapse of the mitochondrial network.