Structure and function of the human mitochondrial MRS2 channel

de Baaij, J. H., Hoenderop, J. G. & Bindels, R. J. Magnesium in man: implications for health and disease. Physiol. Rev. 95, 1–46 (2015).

Article  PubMed  Google Scholar 

Jin, F., Huang, Y. & Hattori, M. Recent advances in the structural biology of Mg(2+) channels and transporters. J. Mol. Biol. 434, 167729 (2022).

Article  CAS  PubMed  Google Scholar 

Quamme, G. A. Molecular identification of ancient and modern mammalian magnesium transporters. Am. J. Physiol. Cell Physiol. 298, C407–C429 (2010).

Article  CAS  PubMed  Google Scholar 

Wiesenberger, G., Waldherr, M. & Schweyen, R. J. The nuclear gene MRS2 is essential for the excision of group II introns from yeast mitochondrial transcripts in vivo. J. Biol. Chem. 267, 6963–6969 (1992).

Article  CAS  PubMed  Google Scholar 

Zsurka, G., Gregan, J. & Schweyen, R. J. The human mitochondrial Mrs2 protein functionally substitutes for its yeast homologue, a candidate magnesium transporter. Genomics 72, 158–168 (2001).

Article  CAS  PubMed  Google Scholar 

Bui, D. M., Gregan, J., Jarosch, E., Ragnini, A. & Schweyen, R. J. The bacterial magnesium transporter CorA can functionally substitute for its putative homologue Mrs2p in the yeast inner mitochondrial membrane. J. Biol. Chem. 274, 20438–20443 (1999).

Article  CAS  PubMed  Google Scholar 

Gregan, J., Kolisek, M. & Schweyen, R. J. Mitochondrial Mg(2+) homeostasis is critical for group II intron splicing in vivo. Genes Dev. 15, 2229–2237 (2001).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kolisek, M. et al. Mrs2p is an essential component of the major electrophoretic Mg2+ influx system in mitochondria. EMBO J. 22, 1235–1244 (2003).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schindl, R., Weghuber, J., Romanin, C. & Schweyen, R. J. Mrs2p forms a high conductance Mg2+ selective channel in mitochondria. Biophys. J. 93, 3872–3883 (2007).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Daw, C. C. et al. Lactate elicits ER-mitochondrial Mg2+ dynamics to integrate cellular metabolism. Cell 183, 474–489.e17 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Piskacek, M., Zotova, L., Zsurka, G. & Schweyen, R. J. Conditional knockdown of hMRS2 results in loss of mitochondrial Mg(2+) uptake and cell death. J. Cell. Mol. Med. 13, 693–700 (2009).

Article  CAS  PubMed  Google Scholar 

Kuramoto, T. et al. A mutation in the gene encoding mitochondrial Mg2+ channel MRS2 results in demyelination in the rat. PLoS Genet. 7, e1001262 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Madaris, T. R. et al. Limiting Mrs2-dependent mitochondrial Mg(2+) uptake induces metabolic programming in prolonged dietary stress. Cell Rep. 42, 112155 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhao, Y. et al. Differentially expressed gene profiles between multidrug resistant gastric adenocarcinoma cells and their parental cells. Cancer Lett. 185, 211–218 (2002).

Article  CAS  PubMed  Google Scholar 

Chen, Y. et al. Human mitochondrial Mrs2 protein promotes multidrug resistance in gastric cancer cells by regulating p27, cyclin D1 expression and cytochrome C release. Cancer Biol. Ther. 8, 607–614 (2009).

Article  CAS  PubMed  Google Scholar 

Yamanaka, R. et al. Mitochondrial Mg(2+) homeostasis decides cellular energy metabolism and vulnerability to stress. Sci. Rep. 6, 30027 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Franken, G. A. C., Huynen, M. A., Martinez-Cruz, L. A., Bindels, R. J. M. & de Baaij, J. H. F. Structural and functional comparison of magnesium transporters throughout evolution. Cell. Mol. Life Sci. 79, 418 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lunin, V. V. et al. Crystal structure of the CorA Mg2+ transporter. Nature 440, 833–837 (2006).

Article  CAS  PubMed  Google Scholar 

Payandeh, J. & Pai, E. F. A structural basis for Mg2+ homeostasis and the CorA translocation cycle. EMBO J. 25, 3762–3773 (2006).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Eshaghi, S. et al. Crystal structure of a divalent metal ion transporter CorA at 2.9 angstrom resolution. Science 313, 354–357 (2006).

Article  CAS  PubMed  Google Scholar 

Guskov, A. et al. Structural insights into the mechanisms of Mg2+ uptake, transport, and gating by CorA. Proc. Natl Acad. Sci. USA 109, 18459–18464 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dalmas, O. et al. A repulsion mechanism explains magnesium permeation and selectivity in CorA. Proc. Natl Acad. Sci. USA 111, 3002–3007 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dalmas, O., Sompornpisut, P., Bezanilla, F. & Perozo, E. Molecular mechanism of Mg2+ -dependent gating in CorA. Nat. Commun. 5, 3590 (2014).

Article  PubMed  Google Scholar 

Matthies, D. et al. Cryo-EM structures of the magnesium channel CorA reveal symmetry break upon gating. Cell 164, 747–756 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rangl, M., Schmandt, N., Perozo, E. & Scheuring, S. Real time dynamics of gating-related conformational changes in CorA. Elife 8, e47322 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lee, A. et al. Ca2+/calmodulin binds to and modulates P/Q-type calcium channels. Nature 399, 155–159 (1999).

Article  CAS  PubMed  Google Scholar 

Imredy, J. P. & Yue, D. T. Mechanism of Ca(2+)-sensitive inactivation of L-type Ca2+ channels. Neuron 12, 1301–1318 (1994).

Article  CAS  PubMed  Google Scholar 

Diwan, J. J., Daze, M., Richardson, R. & Aronson, D. Kinetics of Mg2+ flux into rat liver mitochondria. Biochemistry 18, 2590–2595 (1979).

Article  CAS  PubMed  Google Scholar 

Brierley, G. P., Davis, M. & Jung, D. W. Respiration-dependent uptake and extrusion of Mg2+ by isolated heart mitochondria. Arch. Biochem. Biophys. 253, 322–332 (1987).

Article  CAS  PubMed  Google Scholar 

Bragadin, M., Pozzan, T. & Azzone, G. F. Kinetics of Ca2+ carrier in rat liver mitochondria. Biochemistry 18, 5972–5978 (1979).

Article  CAS  PubMed  Google Scholar 

Comments (0)

No login
gif