2026-08-05 ミュンヘン大学（LMU）
＜関連情報＞
- https://www.lmu.de/en/newsroom/news-overview/news/ion-channel-identified-as-key-factor-in-iron-metabolism-65aa69d2.html
- https://www.pnas.org/doi/10.1073/pnas.2602941123
TPC1依存的なエンドソームpHおよびトランスフェリン取り込みの制御が細胞内鉄状態を決定する TPC1-dependent control of endosomal pH and transferrin uptake determines cellular iron status
Rebecca Deutsch, Simone Jörs, Yvonne Klingl, +22 , and Christian Grimm
Proceedings of the National Academy of Sciences Published:August 5, 2026
DOI:https://doi.org/10.1073/pnas.2602941123
Abstract
Iron overload is a life-threatening disease. Without early diagnosis and treatment, it can cause severe organ damage and even premature death by irreversibly damaging organs such as the heart, pancreas, spleen, or liver. We report here that a gain-of-function mutation in the endolysosomal two-pore channel TPC1 (TPC1I486T) causes iron overload in mice, whereas mice lacking TPC1 exhibit the opposite phenotype, iron deficiency. Endolysosomal patch-clamp experiments demonstrated a strong gain in both human and mouse TPC1 mutant channel activity compared to wild-type upon activation with the early endosome (EE) associated endogenous ligand phosphatidylinositol 3-phosphate. Mechanistically, it was found that uptake of iron bound to transferrin/transferrin receptor from the plasma membrane as well as the pH in EE, from where Fe2+ is being released via DMT1 in a H+ dependent manner strongly depend on TPC1 activity.
