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Updated: Sep 2, 2025

Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome
Published on: November 30, 2022
Lipid droplets promote efficient mitophagy
Maeve Long1, Thomas G McWilliams1,2
1Translational Stem Cell Biology & Metabolism Program, Research Programs Unit, Faculty of Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Abstract:
Mitophagy neutralizes defective mitochondria via lysosomal elimination. Increased levels of mitophagy hallmark metabolic transitions and are induced by iron depletion, yet its metabolic basis has not been studied in-depth. How mitophagy integrates with different homeostatic mechanisms to support metabolic integrity is incompletely understood. We examined metabolic adaptations in cells treated with deferiprone (DFP), a therapeutic iron chelator known to induce PINK1-PRKN-independent mitophagy. We found that iron depletion profoundly rewired the cellular metabolome, remodeling lipid metabolism within minutes of treatment. DGAT1-dependent lipid droplet biosynthesis occurs upstream of mitochondrial turnover, with many LDs bordering mitochondria upon iron chelation. Surprisingly, DGAT1 inhibition restricts mitophagy in vitro by lysosomal dysfunction. Genetic depletion of mdy/DGAT1 in vivo impairs neuronal mitophagy and locomotor function in Drosophila, demonstrating the physiological relevance of our findings.
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