High-content screening identifies FDA-approved activators of mitophagy

High-content screening of 1,971 FDA-approved compounds identified nine that increased mitolysosome numbers while preserving cell viability and mitochondrial integrity.

• Why it matters: Mitochondrial diseases have limited treatments, and activating mitophagy is a promising strategy even when genetic causes differ.
• What they did: Cells with reporters for TFEB nuclear translocation and mitophagy were screened, yielding 294 TFEB-translocating hits and nine mitophagy-promoting candidates.
• The result: In patient fibroblasts, Meptazinol and Ponatinib were top-ranked mitophagy inducers for complex I and IV deficiency, but neither rescued the OXPHOS bioenergetic defect.

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