Tim50, a component of the mitochondrial translocator, regulates mitochondrial integrity and cell death.
In yeast, Tim50 along with Tim23 regulate translocation of presequence-containing proteins across the mitochondrial inner membrane. Here, we describe the identification and characterization of a novel human mitochondrial inner membrane protein homologous to the yeast Tim50. We demonstrate that human Tim50 possesses phosphatase activity and is present in a complex ... with human Tim23. Down-regulation of human Tim50 expression by RNA interference increases the sensitivity of human cell lines to death stimuli by accelerating the release of cytochrome c from the mitochondria. Furthermore, injection of Tim50-specific morpholino antisense oligonucleotides during early zebrafish embryonic development causes neurodegeneration, dysmorphic hearts, and reduced motility as a result of increased cell death. These observations indicate that loss of Tim50 in vertebrates causes mitochondrial membrane permeabilization and dysfunction followed by cytoplasmic release of cytochrome c along with other mitochondrial inducers of cell death. Thus Tim50 is important for both mitochondrial function and early neuronal development.
Mesh Terms:
Acridine Orange, Amino Acid Sequence, Animals, Apoptosis, Carrier Proteins, Cell Death, Cell Line, Cell Line, Tumor, Cell Membrane, Cytochromes c, DNA, Complementary, Down-Regulation, Genetic Vectors, Humans, Hydrogen-Ion Concentration, Immunoblotting, In Situ Hybridization, Membrane Proteins, Membrane Transport Proteins, Mice, Microscopy, Fluorescence, Mitochondria, Mitochondrial Membrane Transport Proteins, Molecular Sequence Data, Neurons, Oligonucleotides, Precipitin Tests, Protein Binding, Protein Conformation, Protein Structure, Tertiary, RNA Interference, RNA, Small Interfering, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid, Staurosporine, Subcellular Fractions, Substrate Specificity, Tissue Distribution, Transfection, Trypsin, Two-Hybrid System Techniques, Ultraviolet Rays, Zebrafish
Acridine Orange, Amino Acid Sequence, Animals, Apoptosis, Carrier Proteins, Cell Death, Cell Line, Cell Line, Tumor, Cell Membrane, Cytochromes c, DNA, Complementary, Down-Regulation, Genetic Vectors, Humans, Hydrogen-Ion Concentration, Immunoblotting, In Situ Hybridization, Membrane Proteins, Membrane Transport Proteins, Mice, Microscopy, Fluorescence, Mitochondria, Mitochondrial Membrane Transport Proteins, Molecular Sequence Data, Neurons, Oligonucleotides, Precipitin Tests, Protein Binding, Protein Conformation, Protein Structure, Tertiary, RNA Interference, RNA, Small Interfering, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid, Staurosporine, Subcellular Fractions, Substrate Specificity, Tissue Distribution, Transfection, Trypsin, Two-Hybrid System Techniques, Ultraviolet Rays, Zebrafish
J. Biol. Chem.
Date: Jun. 04, 2004
PubMed ID: 15044455
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