|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.
|Source:||The Journal of biological chemistry 279(23): 24813-24825 (Journal)|
|Registered Authors:||Farber, Steven|
|PubMed:||15044455 Full text @ J. Biol. Chem.|
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.
ABSTRACTIn 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.