Work

Direct targeting of mitochondria by cisplatin leads to cytotoxicity in zebrafish lateral-line hair cells

Year: 2024

Type: article

Abstract: live imaging of hair cells in the zebrafish lateral-line organ expressing a genetically encoded indicator of cumulative mitochondrial activity, we first demonstrate that greater redox history increases susceptibility to cisplatin. Next, we conducted time-lapse imaging to understand dynamic changes in mitochondrial homeostasis and observe elevated mitochondrial and cytosolic calcium that surge prior to hair cell death. Furthermore, using a localized probe that fluoresces in the presence of cisplatin, we show that cisplatin directly accumulates in hair cell mitochondria, and this accumulation occurs before mitochondrial dysregulation and apoptosis. Our findings provide evidence that cisplatin directly targets hair cell mitochondria and support that the mitochondria are integral to cisplatin cytotoxicity in hair cells.

Source: iScience

DOI: 10.1016/j.isci.2024.110975

Authors: David S. Lee, Angela Schrader, Jiaoxia Zou, Wee Han Ang, Mark E. Warchol, Lavinia Sheets

Institutions: Washington University in St. Louis, National University of Singapore

Language: English

Topic: Hearing, Cochlea, Tinnitus, Genetics

Subfield: Sensory Systems

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,150