Mitochondrial transfer protects against cisplatin-induced hearing loss by fumarate-mediated activation of mitophagy
Year: 2026
Type: article
Abstract: Sensorineural hearing loss (SNHL) affects millions of individuals worldwide, with platinum-based chemotherapeutics identified as a significant cause. In this study, we elucidate the mechanism by which mitochondrial transfer from mesenchymal stem/stromal cells (MSCs) protects against cisplatin-induced cochlear injury in a mouse model. Systemically administered MSCs home to the cochlea and transfer mitochondria to damaged spiral ganglion neurons (SGNs) via tunneling nanotubes, leading to elevated intracellular levels of the Krebs cycle intermediate fumarate, which activates mitophagy to eliminate dysfunctional mitochondria. Mechanistically, dimethyl fumarate (DMF)-a clinically available fumarate derivative-covalently modifies the phosphatase PPP1CB at cysteine 126, thereby blocking PPP1CB-mediated dephosphorylation of mitofusin 2 (MFN2), which in turn enhances mitophagy and ultimately preserves auditory function. These findings reveal that MSCs orchestrate mitochondrial replacement in damaged SGNs by delivering healthy mitochondria and facilitating the removal of impaired ones, underscoring the therapeutic potential of this strategy for treating SNHL related to mitochondrial dysfunction.
Source: Cell Reports
Institutions: Shandong Provincial Hospital, Shandong First Medical University, China Pharmaceutical University, State Key Laboratory of Natural Medicine, Northern Jiangsu People's Hospital, Qilu Hospital of Shandong University, Nanjing Medical University, University of Otago, State Key Laboratory of Digital Medical Engineering, Southeast University
Language: English
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
OpenAlex ID: W7220864869