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This article has been peer reviewed. It was published in: Antioxidants and Redox Signaling.

Volume 19, Issue 6, 20 August 2013, Pages 583-594.

The published version is available at DOI: 10.1089/ars.2012.5171

Copyright © Mary Ann Liebert, Inc.


SIGNIFICANCE: Both transfer RNA (tRNA) and cytochrome c are essential molecules for the survival of cells. tRNA decodes mRNA codons into amino-acid-building blocks in protein in all organisms, whereas cytochrome c functions in the electron transport chain that powers ATP synthesis in mitochondrion-containing eukaryotes. Additionally, in vertebrates, cytochrome c that is released from mitochondria is a potent inducer of apoptosis, activating apoptotic proteins (caspases) in the cytoplasm to dismantle cells. A better understanding of both tRNA and cytochrome c is essential for an insight into the regulation of cell life and death.

RECENT ADVANCES: A recent study showed that the mitochondrion-released cytochrome c can be removed from the cell-death pathway by tRNA molecules. The direct binding of cytochrome c by tRNA provides a mechanism for tRNA to regulate cell death, beyond its role in gene expression.

CRITICAL ISSUES: The nature of the tRNA-cytochrome c binding interaction remains unknown. The questions of how this interaction affects tRNA function, cellular metabolism, and apoptotic sensitivity are unanswered.

FUTURE DIRECTIONS: Investigations into the critical issues raised above will improve the understanding of tRNA in the fundamental processes of cell death and metabolism. Such knowledge will inform therapies in cell death-related diseases.

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