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Publication : Tim50, a component of the mitochondrial translocator, regulates mitochondrial integrity and cell death.

First Author  Guo Y Year  2004
Journal  J Biol Chem Volume  279
Issue  23 Pages  24813-25
PubMed ID  15044455 Mgi Jnum  J:90428
Mgi Id  MGI:3043540 Doi  10.1074/jbc.M402049200
Citation  Guo Y, et al. (2004) Tim50, a component of the mitochondrial translocator, regulates mitochondrial integrity and cell death. J Biol Chem 279(23):24813-25
abstractText  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.
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