The Multifaceted Roles of Proline in Cell Behavior

Herein, we review the multifaceted roles of proline in cell biology. This peculiar cyclic imino acid is: (i) A main precursor of extracellular collagens (the most abundant human proteins), antimicrobial peptides (involved in innate immunity), salivary proteins (astringency, teeth health) and cornifins (skin permeability); (ii) an energy source for pathogenic bacteria, protozoan parasites, and metastatic cancer cells, which engage in extracellular-protein degradation to invade their host; (iii) an antistress molecule (an osmolyte and chemical chaperone) helpful against various potential harms (UV radiation, drought/salinity, heavy metals, reactive oxygen species); (iv) a neural metabotoxin associated with schizophrenia; (v) a modulator of cell signaling pathways such as the amino acid stress response and extracellular signal-related kinase pathway; (vi) an epigenetic modifier able to promote DNA and histone hypermethylation; (vii) an inducer of proliferation of stem and tumor cells; and (viii) a modulator of cell morphology and migration/invasiveness. We highlight how proline metabolism impacts beneficial tissue regeneration, but also contributes to the progression of devastating pathologies such as fibrosis and metastatic cancer.

Automated summary

Proline plays multifaceted roles in cell biology, serving as a precursor of extracellular proteins, an energy source, an antistress molecule, a neural metabotoxin, a modulator of cell signaling pathways, an epigenetic modifier, an inducer of cell proliferation, and a modulator of cell morphology and migration/invasiveness. Proline metabolism impacts beneficial tissue regeneration but also contributes to the progression of devastating pathologies such as fibrosis and metastatic cancer.