Unresolved Questions from the Analysis of Mice Lacking MCU Expression

Overview

Journal Biochem Biophys Res Commun

Publisher Elsevier

Specialty Biochemistry

Date 2014 May 6

PMID 24792186

Citations 69

Authors

Elizabeth Murphy

Xin Pan

Tiffany Nguyen

Jie Liu

Kira M Holmstrom

Toren Finkel

Affiliations

Soon will be listed here.

Abstract

Entry of mitochondrial calcium is believed to play an essential role in regulating bioenergetics and initiating cell death pathways. We have recently described a mouse model lacking MCU expression. Surprisingly, these mice are viable and the cells and tissues from these animals do not exhibit any marked protection from cell death. Here, we discuss our findings as well as potential explanations for some of the more unexpected results.

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References

Pan X, Liu J, Nguyen T, Liu C, Sun J, Teng Y . The physiological role of mitochondrial calcium revealed by mice lacking the mitochondrial calcium uniporter. Nat Cell Biol. 2013; 15(12):1464-72. PMC: 3852190. DOI: 10.1038/ncb2868. View

Garcia-Dorado D, Ruiz-Meana M, Inserte J, Rodriguez-Sinovas A, Piper H . Calcium-mediated cell death during myocardial reperfusion. Cardiovasc Res. 2012; 94(2):168-80. DOI: 10.1093/cvr/cvs116. View

Garcia-Rivas G, Carvajal K, Correa F, Zazueta C . Ru360, a specific mitochondrial calcium uptake inhibitor, improves cardiac post-ischaemic functional recovery in rats in vivo. Br J Pharmacol. 2006; 149(7):829-37. PMC: 2014682. DOI: 10.1038/sj.bjp.0706932. View

Yu S, Yu D, Lee E, Eckhaus M, Lee R, Corria Z . Variable and tissue-specific hormone resistance in heterotrimeric Gs protein alpha-subunit (Gsalpha) knockout mice is due to tissue-specific imprinting of the gsalpha gene. Proc Natl Acad Sci U S A. 1998; 95(15):8715-20. PMC: 21142. DOI: 10.1073/pnas.95.15.8715. View

Joiner M, Koval O, Li J, He B, Allamargot C, Gao Z . CaMKII determines mitochondrial stress responses in heart. Nature. 2012; 491(7423):269-73. PMC: 3471377. DOI: 10.1038/nature11444. View

Linkermann A, Brasen J, Darding M, Jin M, Sanz A, Heller J . Two independent pathways of regulated necrosis mediate ischemia-reperfusion injury. Proc Natl Acad Sci U S A. 2013; 110(29):12024-9. PMC: 3718149. DOI: 10.1073/pnas.1305538110. View

Feng S, Li H, Tai Y, Huang J, Su Y, Abramowitz J . Canonical transient receptor potential 3 channels regulate mitochondrial calcium uptake. Proc Natl Acad Sci U S A. 2013; 110(27):11011-6. PMC: 3704010. DOI: 10.1073/pnas.1309531110. View

Juhaszova M, Wang S, Zorov D, Nuss H, Gleichmann M, Mattson M . The identity and regulation of the mitochondrial permeability transition pore: where the known meets the unknown. Ann N Y Acad Sci. 2008; 1123:197-212. DOI: 10.1196/annals.1420.023. View

Piot C, Croisille P, Staat P, Thibault H, Rioufol G, Mewton N . Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N Engl J Med. 2008; 359(5):473-81. DOI: 10.1056/NEJMoa071142. View

10.

Shull M, Ormsby I, Kier A, Pawlowski S, Diebold R, Yin M . Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature. 1992; 359(6397):693-9. PMC: 3889166. DOI: 10.1038/359693a0. View

11.

Kim J, Jin Y, Lemasters J . Reactive oxygen species, but not Ca2+ overloading, trigger pH- and mitochondrial permeability transition-dependent death of adult rat myocytes after ischemia-reperfusion. Am J Physiol Heart Circ Physiol. 2006; 290(5):H2024-34. DOI: 10.1152/ajpheart.00683.2005. View

12.

Baines C, Kaiser R, Purcell N, Blair N, Osinska H, Hambleton M . Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature. 2005; 434(7033):658-62. DOI: 10.1038/nature03434. View

13.

Bertossi A, Aichinger M, Sansonetti P, Lech M, Neff F, Pal M . Loss of Roquin induces early death and immune deregulation but not autoimmunity. J Exp Med. 2011; 208(9):1749-56. PMC: 3171092. DOI: 10.1084/jem.20110578. View