TRPM7 senses oxidative stress to release Zn2+ from unique intracellular vesicles

Sunday A. Abiria, Grigory Krapivinsky, Rajan Sah, Ana G. Santa-Cruz, Dipayan Chaudhuri, Jin Zhang, Pichet Adstamongkonkul, Paul G. Decaen, David E. Clapham

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


TRPM7 (transient receptor potential cation channel subfamily M member 7) regulates gene expression and stress-induced cytotox-icity and is required in early embryogenesis through organ development. Here, we show that the majority of TRPM7 is localized in abundant intracellular vesicles. These vesicles (M7Vs) are distinct from endosomes, lysosomes, and other familiar vesicles or organelles. M7Vs accumulate Zn2+ in a glutathione-enriched, reduced lumen when cytosolic Zn2+ concentrations are elevated. Treatments that increase reactive oxygen species (ROS) trigger TRPM7-dependent Zn2+ release from the vesicles, whereas reduced glutathione prevents TRPM7-dependent cytosolic Zn2+ influx. These observations strongly support the notion that ROS-mediated TRPM7 activation releases Zn2+ from intracellular vesicles after Zn2+ overload. Like the endoplasmic reticulum, these vesicles are a distributed system for divalent cation uptake and release, but in this case the primary divalent ion is Zn2+ rather than Ca2+.

Original languageEnglish
Pages (from-to)E6079-E6088
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number30
StatePublished - Jul 25 2017


  • TRPM7
  • Vesicles
  • Zinc


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