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