TY - JOUR
T1 - Molecular basis and consequences of the cytochrome c-tRNA interaction
AU - Liu, Cuiping
AU - Stonestrom, Aaron J.
AU - Christian, Thomas
AU - Yong, Jeongsik
AU - Takase, Ryuichi
AU - Hou, Ya Ming
AU - Yang, Xiaolu
N1 - Publisher Copyright:
© 2016 by The American Society for Biochemistry and Molecular Biology, Inc. Published.
PY - 2016/5/6
Y1 - 2016/5/6
N2 - The intrinsic apoptosis pathway occurs through the release of mitochondrial cytochrome c to the cytosol, where it promotes activation of the caspase family of proteases. The observation that tRNA binds to cytochrome c revealed a previously unexpected mode of apoptotic regulation. However, the molecular characteristics of this interaction, and its impact on each interaction partner, are not well understood. Using a novel fluorescence assay, we show here that cytochrome c binds to tRNA with an affinity comparable with other tRNA-protein binding interactions and with a molecular ratio of∼3:1. Cytochrome c recognizes the tertiary structural features of tRNA, particularly in the core region. This binding is independent of the charging state of tRNA but is regulated by the redox state of cytochrome c. Compared with reduced cytochrome c, oxidized cytochrome c binds to tRNA with a weaker affinity, which correlates with its stronger pro-apoptotic activity. tRNA binding both facilitates cytochrome c reduction and inhibits the peroxidase activity of cytochrome c, which is involved in its release from mitochondria. Together, these findings provide new insights into the cytochrome c-tRNA interaction and apoptotic regulation.
AB - The intrinsic apoptosis pathway occurs through the release of mitochondrial cytochrome c to the cytosol, where it promotes activation of the caspase family of proteases. The observation that tRNA binds to cytochrome c revealed a previously unexpected mode of apoptotic regulation. However, the molecular characteristics of this interaction, and its impact on each interaction partner, are not well understood. Using a novel fluorescence assay, we show here that cytochrome c binds to tRNA with an affinity comparable with other tRNA-protein binding interactions and with a molecular ratio of∼3:1. Cytochrome c recognizes the tertiary structural features of tRNA, particularly in the core region. This binding is independent of the charging state of tRNA but is regulated by the redox state of cytochrome c. Compared with reduced cytochrome c, oxidized cytochrome c binds to tRNA with a weaker affinity, which correlates with its stronger pro-apoptotic activity. tRNA binding both facilitates cytochrome c reduction and inhibits the peroxidase activity of cytochrome c, which is involved in its release from mitochondria. Together, these findings provide new insights into the cytochrome c-tRNA interaction and apoptotic regulation.
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U2 - 10.1074/jbc.M115.697789
DO - 10.1074/jbc.M115.697789
M3 - Article
C2 - 26961879
AN - SCOPUS:84966348919
SN - 0021-9258
VL - 291
SP - 10426
EP - 10436
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 19
ER -