The study published in the Proceedings of the National Academy of Sciences (PNAS) today reveals that endosomes act as autonomous calcium reservoirs, contradicting the traditional view of the endoplasmic reticulum and lysosomes as the sole commanders of intracellular calcium storage. Researchers found that Two-pore channel 1 (TPC1) in endosomes releases localized calcium bursts, or nanodomains, which specifically orchestrate the trafficking of transferrin receptors and control iron homeostasis. The findings, showing that TPC1 inactivation leads to iron-deficient phenotypes, redefines endosomes as mobilizable calcium stores and dynamic signalling hubs rather than simple sorting stations, opening new therapeutic avenues for metabolic disorders and anaemia.
Lead author Dr Will Burton, who successfully defended his DPhil viva in July, said: “Using newly validated TPC1 selectivity filter and ‘lipid-insensitive’ mutant constructs to investigate the circuitry of TPC1, I am pleased to share our findings identifying a novel role for TPC1 in iron trafficking and homeostasis. We hope these new tools and findings will prove valuable for future studies characterising the functional role of the relatively understudied TPC1 isoform in endosomal physiology and intracellular signalling pathways.”
- Endosomal TPC1-mediated Ca2+ nanodomains regulate transferrin receptor trafficking and iron homeostasis. William J Burton , Alice Lin, Anthony J Morgan, Lianne C Davis, Cheng-Chang Chen, Antony Galione. Proc Natl Acad Sci U S A (2026) Jul 21;123(29):e2530835123. doi: 10.1073/pnas.2530835123. Epub 2026 Jul 15. For more details, explore the research findings in PNAS https://www.pnas.org/doi/10.1073/pnas.2530835123