Intracellular peptides: From discovery to function

•Many intracellular peptides are generated by the proteasome and other intracellular enzymes.•Some intracellular peptides resist degradation by aminopeptidases.•Intracellular peptides are important bioactive molecules performing various functions.

Peptidomics techniques have identified hundreds of peptides that are derived from proteins present mainly in the cytosol, mitochondria, and/or nucleus; these are termed intracellular peptides to distinguish them from secretory pathway peptides that function primarily outside of the cell. The proteasome and thimet oligopeptidase participate in the production and metabolism of intracellular peptides. Many of the intracellular peptides are common among mouse tissues and human cell lines analyzed and likely to perform a variety of functions within cells. Demonstrated functions include the modulation of signal transduction, mitochondrial stress, and development; additional functions will likely be found for intracellular peptides.

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