A key role for Mg2+in TRPM7's control of ROS levels during cell stress

Hsiang Chin Chen, Li Ting Su, Omayra González-Pagán, Jeffrey D. Overton, Loren W. Runnels

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


The TRPM7 (transient receptor potential melastatin 7) channel has been shown to play a pivotal role in cell survival during brain ischaemia as well as in the survival of other cell types challenged with apoptotic stimuli. Ca 2+ is thought to be central to the channel's ability to regulate ROS (reactive oxygen species) production. However, channel-mediated entry of Mg 2+ and Zn2+have also been implicated in cell death. In the present study, we show that depletion of TRPM7 by RNA interference in fibroblasts increases cell resistance to apoptotic stimuli by decreasing ROS levels in an Mg2+ -dependent manner. Depletion of TRPM7 lowered cellular Mg2+ , decreased the concentration of ROS and lessened p38 MAPK (mitogen-activated protein kinase) and JNK (c-Jun N-terminal kinase) activation as well as decreased caspase 3 activation and PARP [poly(ADP-ribose) polymerase] cleavage in response to apoptotic stimuli. Re-expression of TRPM7 or of a kinase-inactive mutant of TRPM7 in TRPM7-knockdown cells increased cellular Mg2+ and ROS levels, as did expression of the Mg 2+ transporter SLC41A2 (solute carrier family 41 member 2). In addition, expression of SLC41A2 increased the sensitivity of TRPM7-knockdown cells to apoptotic stimuli and boosted ROS generation in response to cell stress. Taken together, these data uncover an essential role for Mg2+ in TRPM7's control of cell survival and in the regulation of cellular ROS levels.

Original languageEnglish (US)
Pages (from-to)441-448
Number of pages8
JournalBiochemical Journal
Issue number3
StatePublished - Aug 1 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


  • Apoptosis
  • Cell stress
  • Mg
  • Reactive oxygen species (ROS)
  • Transient receptor potential melastatin 7 (TRPM7)


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