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

ABSTRACT: Cisplatin is a chemotherapy drug that causes permanent hearing loss by injuring cochlear hair cells. Hair cell mitochondria have emerged as potential mediators of hair cell cytotoxicity. Using in vivo 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 accumul

SUBMITTER: Lee DS 

PROVIDER: S-EPMC11466657 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature