Back to Search
Start Over
The LETM1/YOL027 gene family encodes a factor of the mitochondrial K+ homeostasis with a potential role in the Wolf-Hirschhorn syndrome.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2004 Jul 16; Vol. 279 (29), pp. 30307-15. Date of Electronic Publication: 2004 May 11. - Publication Year :
- 2004
-
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.
- Subjects :
- Amino Acid Sequence
Animals
Calcium-Binding Proteins genetics
Cloning, Molecular
DNA, Complementary metabolism
Gene Deletion
Green Fluorescent Proteins
Homeostasis
Humans
Intracellular Membranes metabolism
Luminescent Proteins metabolism
Membrane Potentials
Membrane Proteins genetics
Microscopy, Confocal
Microscopy, Electron
Microscopy, Fluorescence
Mitochondrial Proteins
Molecular Sequence Data
Mutation
Phenotype
Plasmids metabolism
Potassium chemistry
Potassium Acetate pharmacology
Saccharomyces cerevisiae metabolism
Saccharomyces cerevisiae Proteins genetics
Sequence Homology, Amino Acid
Subcellular Fractions metabolism
Syndrome
Time Factors
Calcium-Binding Proteins metabolism
Membrane Proteins metabolism
Mitochondria metabolism
Multigene Family
Muscular Diseases genetics
Potassium metabolism
Saccharomyces cerevisiae Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 279
- Issue :
- 29
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 15138253
- Full Text :
- https://doi.org/10.1074/jbc.M403607200