LETM1 explained

Leucine zipper-EF-hand containing transmembrane protein 1 is a protein that in humans is encoded by the LETM1 gene.^[1]

Structure

The LETM1 protein has a transmembrane domain and a casein kinase 2 and protein kinase C phosphorylation site.^[2] The LETM1 gene is expressed in the mitochondria of many eukaryotes indicating that this is a conserved mitochondrial protein.^[3]

Function

LETM1 is a eukaryotic protein that is expressed in the inner membrane of mitochondria. Experiments performed with human cells have been interpreted to indicate that it functions as a component of a Ca²⁺/H⁺ antiporter.^[4] Experimental results with yeast cells have been interpreted as suggesting that LETM1 functions as a component of a K⁺/H⁺ antiporter.^[5] The Drosophila melanogaster LETM1 protein has been shown to functionally substitute for the K⁺/H⁺ antiporter function in yeast cells.^[6]

Clinical significance

Deletion of LETM1 is thought to be involved in the development of Wolf–Hirschhorn syndrome in humans.^[2]

See also

• LETM1-like protein family

Further reading

• Piao L, Li Y, Kim SJ, Byun HS, Huang SM, Hwang SK, Yang KJ, Park KA, Won M, Hong J, Hur GM, Seok JH, Shong M, Cho MH, Brazil DP, Hemmings BA, Park J . Association of LETM1 and MRPL36 contributes to the regulation of mitochondrial ATP production and necrotic cell death . Cancer Research . 69 . 8 . 3397–404 . Apr 2009 . 19318571 . 10.1158/0008-5472.CAN-08-3235 . free .
• Endele S, Fuhry M, Pak SJ, Zabel BU, Winterpacht A . LETM1, a novel gene encoding a putative EF-hand Ca(2+)-binding protein, flanks the Wolf-Hirschhorn syndrome (WHS) critical region and is deleted in most WHS patients . Genomics . 60 . 2 . 218–25 . Sep 1999 . 10486213 . 10.1006/geno.1999.5881 .
• Nowikovsky K, Froschauer EM, Zsurka G, Samaj J, Reipert S, Kolisek M, Wiesenberger G, Schweyen RJ . The LETM1/YOL027 gene family encodes a factor of the mitochondrial K+ homeostasis with a potential role in the Wolf-Hirschhorn syndrome . The Journal of Biological Chemistry . 279 . 29 . 30307–15 . Jul 2004 . 15138253 . 10.1074/jbc.M403607200 . free .
• Tamai S, Iida H, Yokota S, Sayano T, Kiguchiya S, Ishihara N, Hayashi J, Mihara K, Oka T . Characterization of the mitochondrial protein LETM1, which maintains the mitochondrial tubular shapes and interacts with the AAA-ATPase BCS1L . Journal of Cell Science . 121 . Pt 15 . 2588–600 . Aug 2008 . 18628306 . 10.1242/jcs.026625 . free .
• Piao L, Li Y, Kim SJ, Sohn KC, Yang KJ, Park KA, Byun HS, Won M, Hong J, Hur GM, Seok JH, Shong M, Sack R, Brazil DP, Hemmings BA, Park J . Regulation of OPA1-mediated mitochondrial fusion by leucine zipper/EF-hand-containing transmembrane protein-1 plays a role in apoptosis . Cellular Signalling . 21 . 5 . 767–77 . May 2009 . 19168126 . 10.1016/j.cellsig.2009.01.020 .
• Jiang D, Zhao L, Clapham DE . Genome-wide RNAi screen identifies Letm1 as a mitochondrial Ca2+/H+ antiporter . Science . 326 . 5949 . 144–7 . Oct 2009 . 19797662 . 10.1126/science.1175145 . 4067766 . 2009Sci...326..144J .
• Hwang SK, Piao L, Lim HT, Minai-Tehrani A, Yu KN, Ha YC, Chae CH, Lee KH, Beck GR, Park J, Cho MH . Suppression of lung tumorigenesis by leucine zipper/EF hand-containing transmembrane-1 . PLOS ONE . 5 . 9 . 2010 . e12535 . 20824095 . 2932724 . 10.1371/journal.pone.0012535 . 2010PLoSO...512535H . free .
• Dimmer KS, Navoni F, Casarin A, Trevisson E, Endele S, Winterpacht A, Salviati L, Scorrano L . LETM1, deleted in Wolf-Hirschhorn syndrome is required for normal mitochondrial morphology and cellular viability . Human Molecular Genetics . 17 . 2 . 201–14 . Jan 2008 . 17925330 . 10.1093/hmg/ddm297 . free .
• Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J . Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides . Nature Biotechnology . 21 . 5 . 566–9 . May 2003 . 12665801 . 10.1038/nbt810 . 23783563 .
• Hasegawa A, van der Bliek AM . Inverse correlation between expression of the Wolfs Hirschhorn candidate gene Letm1 and mitochondrial volume in C. elegans and in mammalian cells . Human Molecular Genetics . 16 . 17 . 2061–71 . Sep 2007 . 17606466 . 10.1093/hmg/ddm154 . free .
• Hendrickson SL, Lautenberger JA, Chinn LW, Malasky M, Sezgin E, Kingsley LA, Goedert JJ, Kirk GD, Gomperts ED, Buchbinder SP, Troyer JL, O'Brien SJ . Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression . PLOS ONE . 5 . 9 . e12862 . 2010 . 20877624 . 2943476 . 10.1371/journal.pone.0012862 . 2010PLoSO...512862H . free .
• Schlickum S, Moghekar A, Simpson JC, Steglich C, O'Brien RJ, Winterpacht A, Endele SU . LETM1, a gene deleted in Wolf-Hirschhorn syndrome, encodes an evolutionarily conserved mitochondrial protein . Genomics . 83 . 2 . 254–61 . Feb 2004 . 14706454 . 10.1016/j.ygeno.2003.08.013 .
• Barbe L, Lundberg E, Oksvold P, Stenius A, Lewin E, Björling E, Asplund A, Pontén F, Brismar H, Uhlén M, Andersson-Svahn H . Toward a confocal subcellular atlas of the human proteome . Molecular & Cellular Proteomics . 7 . 3 . 499–508 . Mar 2008 . 18029348 . 10.1074/mcp.M700325-MCP200 . free .

Notes and References

1. Web site: Entrez Gene: leucine zipper-EF-hand containing transmembrane protein 1.
2. Endele S, Fuhry M, Pak SJ, Zabel BU, Winterpacht A . LETM1, a novel gene encoding a putative EF-hand Ca(2+)-binding protein, flanks the Wolf-Hirschhorn syndrome (WHS) critical region and is deleted in most WHS patients . Genomics . 60 . 2 . 218–25 . Sep 1999 . 10486213 . 10.1006/geno.1999.5881 .
3. Schlickum S, Moghekar A, Simpson JC, Steglich C, O'Brien RJ, Winterpacht A, Endele SU . LETM1, a gene deleted in Wolf-Hirschhorn syndrome, encodes an evolutionarily conserved mitochondrial protein . Genomics . 83 . 2 . 254–61 . Feb 2004 . 14706454 . 10.1016/j.ygeno.2003.08.013 .
4. Waldeck-Weiermair M, Jean-Quartier C, Rost R, Khan MJ, Vishnu N, Bondarenko AI, Imamura H, Malli R, Graier WF . Leucine zipper EF hand-containing transmembrane protein 1 (Letm1) and uncoupling proteins 2 and 3 (UCP2/3) contribute to two distinct mitochondrial Ca2+ uptake pathways . The Journal of Biological Chemistry . 286 . 32 . 28444–55 . Aug 2011 . 21613221 . 3151087 . 10.1074/jbc.M111.244517 . free .
5. Zotova L, Aleschko M, Sponder G, Baumgartner R, Reipert S, Prinz M, Schweyen RJ, Nowikovsky K . Novel components of an active mitochondrial K(+)/H(+) exchange . The Journal of Biological Chemistry . 285 . 19 . 14399–414 . May 2010 . 20197279 . 2863244 . 10.1074/jbc.M109.059956 . free .
6. McQuibban AG, Joza N, Megighian A, Scorzeto M, Zanini D, Reipert S, Richter C, Schweyen RJ, Nowikovsky K . A Drosophila mutant of LETM1, a candidate gene for seizures in Wolf-Hirschhorn syndrome . Human Molecular Genetics . 19 . 6 . 987–1000 . Mar 2010 . 20026556 . 10.1093/hmg/ddp563 .