PUBLICATION
Tim50, a component of the mitochondrial translocator, regulates mitochondrial integrity and cell death
- Authors
- Guo, Y., Cheong, N., Zhang, Z., De Rose, R., Deng, Y., Farber, S.A., Fernandes-Alnemri, T., Alnemri, E.S.
- ID
- ZDB-PUB-040329-11
- Date
- 2004
- Source
- The Journal of biological chemistry 279(23): 24813-24825 (Journal)
- Registered Authors
- Farber, Steven
- Keywords
- none
- MeSH Terms
-
- Transfection
- Cell Line
- Cell Death
- Cytochromes c/metabolism
- DNA, Complementary/metabolism
- Acridine Orange/pharmacology
- Membrane Transport Proteins/chemistry
- Membrane Transport Proteins/physiology*
- In Situ Hybridization
- Ultraviolet Rays
- Oligonucleotides/chemistry
- Carrier Proteins/chemistry
- Carrier Proteins/physiology*
- Precipitin Tests
- Molecular Sequence Data
- Protein Structure, Tertiary
- Sequence Homology, Amino Acid
- Hydrogen-Ion Concentration
- RNA, Small Interfering/metabolism
- Cell Membrane/metabolism
- Saccharomyces cerevisiae Proteins/chemistry
- Saccharomyces cerevisiae Proteins/physiology*
- Immunoblotting
- Trypsin/chemistry
- Trypsin/pharmacology
- Mitochondrial Membrane Transport Proteins*
- Animals
- Tissue Distribution
- Cell Line, Tumor
- Zebrafish
- Subcellular Fractions
- Genetic Vectors
- Humans
- Mitochondria/metabolism*
- Microscopy, Fluorescence
- Membrane Proteins/chemistry
- Membrane Proteins/physiology*
- Amino Acid Sequence
- Substrate Specificity
- Neurons/metabolism
- Protein Conformation
- Staurosporine/pharmacology
- Mice
- Apoptosis
- RNA Interference
- Two-Hybrid System Techniques
- Protein Binding
- Down-Regulation
- PubMed
- 15044455 Full text @ J. Biol. Chem.
Citation
Guo, Y., Cheong, N., Zhang, Z., De Rose, R., Deng, Y., Farber, S.A., Fernandes-Alnemri, T., Alnemri, E.S. (2004) Tim50, a component of the mitochondrial translocator, regulates mitochondrial integrity and cell death. The Journal of biological chemistry. 279(23):24813-24825.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping