The LETM1/YOL027 gene family encodes a factor of the mitochondrial K+ homeostasis with a potential role in the Wolf-Hirschhorn syndrome.

Abstract	The yeast open reading frames YOL027 and YPR125 and their orthologs in various eukaryotes encode proteins with a single predicted trans-membrane domain ranging in molecular mass from 45 to 85 kDa. Hemizygous deletion of their human homolog LETM1 is likely to contribute to the Wolf-Hirschhorn syndrome phenotype. We show here that in yeast and human cells, these genes encode integral proteins of the inner mitochondrial membrane. Deletion of the yeast YOL027 gene (yol027Delta mutation) results in mitochondrial dysfunction. This mutant phenotype is complemented by the expression of the human LETM1 gene in yeast, indicating a functional conservation of LetM1/Yol027 proteins from yeast to man. Mutant yol027Delta mitochondria have increased cation contents, particularly K+ and low-membrane-potential Deltapsi. They are massively swollen in situ and refractory to potassium acetate-induced swelling in vitro, which is indicative of a defect in K+/H+ exchange activity. Thus, YOL027/LETM1 are the first genes shown to encode factors involved in both K+ homeostasis and organelle volume control.
Authors	Karin Nowikovsky, Elisabeth M Froschauer, Gabor Zsurka, Jozef Samaj, Siegfried Reipert, Martin Kolisek, Gerlinde Wiesenberger, Rudolf J Schweyen
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 279 Issue 29 Pg. 30307-15 (Jul 16 2004) ISSN: 0021-9258 [Print] United States
PMID	15138253 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Calcium-Binding Proteins DNA, Complementary LETM1 protein, human Luminescent Proteins MDM38 protein, S cerevisiae Membrane Proteins Mitochondrial Proteins Saccharomyces cerevisiae Proteins Green Fluorescent Proteins Potassium Acetate Potassium
Topics	Amino Acid Sequence Animals Calcium-Binding Proteins (genetics, metabolism) Cloning, Molecular DNA, Complementary (metabolism) Gene Deletion Green Fluorescent Proteins Homeostasis Humans Intracellular Membranes (metabolism) Luminescent Proteins (metabolism) Membrane Potentials Membrane Proteins (genetics, metabolism) Microscopy, Confocal Microscopy, Electron Microscopy, Fluorescence Mitochondria (metabolism) Mitochondrial Proteins Molecular Sequence Data Multigene Family Muscular Diseases (genetics) Mutation Phenotype Plasmids (metabolism) Potassium (chemistry, metabolism) Potassium Acetate (pharmacology) Saccharomyces cerevisiae (metabolism) Saccharomyces cerevisiae Proteins (genetics, metabolism) Sequence Homology, Amino Acid Subcellular Fractions (metabolism) Syndrome Time Factors

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!