Molecular and physiological characteristics of Na+/Mg2+ exchanger SLC41A1 in HEK293 cells and in primary-derived and KL-1 cardiomyocytes

• Applicant: Dr. Martin Kolisek
• Subject Area: Veterinary Medical Science
• Term: from 2008 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 69876609

• Final Report Year: 2016

Final Report Abstract

In summary the project led to publications primarily describing (1) regulation of SLC41A1 and its detailed molecular biology. Furthermore, (2) in our work we have proposed, apart of its obvious role in intracellular magnesium homeostasis, also role of SLC41A1 in pathophysiology of prominent ailments such as: diabetes mellitus, Parkinson’s disease, and also cancer. In particular the link between SLC41A1 and the regulation of Akt/PKB makes SLC41A1 to be an attractive target for translational medicine and chronobiology in future studies. I believe that work resulting from this project significantly shifted our knowledge on involvement of SLC41A1 in cellular physiology and pathophysiology, and helped to understand also the role of the close homolog of SLC41A1, namely SLC41A3 that is the first ever described Mg2+ carrier and Mg2+-efflux sysem in mitochondria.

Publications

• "Inside-in" or "inside-out"? The membrane topology of SLC41A1. Magnesium Research 2013/26(4)/176-81
  Sponder G, Rutschmann K, Kolisek M
  
• Nature of SLC41A1 complexes: report on split-ubiquitin yeast two hybrid assay. Magnesium Research 2013/26(2)/56-66
  Nestler A, Sponder S, Rutschmann K, Mastrototaro M, Weise C, Vormann J, Schweigel-Röntgen M, Kolisek M
  
• Substitution p.A350V in Na+/Mg2+ exchanger SLC41A1, Potentially associated with Parkinson’s Disease, is a gain of function mutation. PLoS ONE 2013/8(8)/e71096
  Kolisek M, Sponder G, Mastrototaro L, Smorodchenko A, Launay P, Vormann J, Schweigel-Röntgen M
  
• Insulin modulates the Na+/Mg2+ exchanger SLC41A1 and influences Mg2+ efflux from intracellular stores in transgenic HEK293 cells. Journal of Nutrition 2015/145(11)/2440-7
  Mastrototaro L, Tietjen U, Sponder G, Vormann J, Aschenbach JR, Kolisek M
  
• PARK7/DJ-1 dysregulation by oxidative stress leads to magnesium deficiency: implications in degenerative and chronic diseases. Clinical Science 2015/129(12)/1143-50
  Kolisek M, Montezano AM, Sponder G, Anagnastopulou A, Vormann J, Rhian Touyz R, Aschenbach JR
  
• Human CNNM2 is not a Mg2+ transporter per se. Pflügers Archiv – European Jornal of Physiology 2016/23.03 / Epub ahead of print
  Mastrototaro L, Sponder G, Kurth K, Merolle L, Zhang Z, Abdulhanan N, Smorodchenko A, Wolf K, Fleig A, Iotti S, Aschenbach JR, Vormann J, Kolisek M
  
• SLC41A3 encodes for a mitochondrial Mg2+ efflux system. Scientific Reports, 6, Article number: 27999 (2016)
  Mastrototaro L, Smorodchenko A, Aschenbach JR, Kolisek M, Sponder G