Aligned with ferroptosis restricting circulating cancer cells, the BDH2β2,5-DHBA pathway protects mesenchymal cells from ferroptosis in the blood, boosting their capacity to seed secondary organs.
Aligned with ferroptosis restricting circulating cancer cells, the BDH2β2,5-DHBA pathway protects mesenchymal cells from ferroptosis in the blood, boosting their capacity to seed secondary organs.
Restoring BDH2 or supplementing 2,5-DHBA rescues iron transfer, lysosomal pH, and ferroptosis resistance.
When BDH2 is lost, iron gets trapped in lysosomes, lysosomal pH rises, and contacts weaken. As a consequence, mesenchymal cells become highly vulnerable to ferroptosis.
We show that BDH2 is a key regulator of inter-organelle Fe(II) transfer. In melanocytic cells, BDH2 localizes at mitochondriaβlysosome contacts. There it produces the siderophore 2,5-DHBA, which ferries Fe(II) into mitochondria. This supports respiration and lysosomal acidification.
Excited to share my PhD paper out now in Nature Metabolism! π¨ We studied how intracellular iron trafficking controls ferroptosis vulnerability in melanoma. Shout-out to @agostinislab.bsky.social and all collaborators who made this possible! @natmetabolism.nature.com
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Hi Bluesky community ππ»π¦ just moved in! Iβm a PhD student @ VIB (Belgium), interested in iron metabolism, membrane contact sites, ferroptosis, and cancer biology. If this sounds like something for you, take a look at our latest preprint π www.researchsquare.com/article/rs-5...