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Aminoglycoside induces RIPOR2 translocation and phosphatidylserine externalization via distinct mechanisms

Jinan Li1, Michelle Yang1, Bo Zhao1,2,3

  • 1Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN, United States.

Frontiers in Cellular Neuroscience
|August 22, 2025
PubMed

Insights

Aminoglycosides cause hearing loss by damaging cochlear hair cells. This study reveals that aminoglycoside-induced RIPOR2 translocation and phosphatidylserine externalization occur independently, suggesting distinct ototoxicity pathways.

Area of Science:

  • Ototoxicity research
  • Cellular biology
  • Molecular mechanisms of hearing loss

Background:

  • Aminoglycosides (AGs) are crucial for treating severe infections but can cause irreversible hearing loss.
  • AGs induce cochlear hair cell death through RIPOR2 translocation and phosphatidylserine (PS) externalization.
  • The precise relationship between these two events and the role of cisplatin in ototoxicity remain unclear.

Purpose of the Study:

  • To investigate whether AG-induced RIPOR2 translocation and PS externalization are independent events.
  • To explore the effect of PS externalization on RIPOR2 translocation in hair cells.
  • To compare the ototoxic mechanisms of AGs and cisplatin in hair cells.

Main Methods:

  • Treatment of wild-type hair cells with AGs over varying time points.
  • Investigation of RIPOR2 localization and PS externalization.
  • Assessment of cisplatin's effects on PS externalization and RIPOR2 localization.

Main Results:

  • AGs trigger RIPOR2 translocation and PS externalization through independent molecular pathways.
  • PS externalization does not appear to influence AG-induced RIPOR2 translocation.
  • Cisplatin and AGs induce hair cell death via distinct molecular pathways, despite shared ototoxic features.

Conclusions:

  • AG-induced ototoxicity involves parallel molecular pathways for RIPOR2 translocation and PS externalization.
  • Cisplatin and AGs represent distinct mechanisms of hair cell damage.
  • Understanding these distinct pathways may inform strategies to mitigate drug-induced hearing loss.
Keywords:
RIPOR2aminoglycosidehair cellmechanotransductionototoxicityphosphatidylserine

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