Yiwei Huang

Gating strategy and knockdown efficiency.

RETSAT links retinoid metabolism to ferroptosis.

RETSAT is a pro-ferroptosis gene.

RETSAT mediates ferroptosis by activating the retinoic acid receptor pathway.

RETSAT does not interfere with known ferroptosis regulators.

RETSAT-RAR pathway promotes ferroptosis by activating SCD-mediated MUFA generation.

The legends for supplementary figure 1-7.

RETSAT-RAR-SCD signaling pathway regulates ferroptosis via MUFA generation, and targeting retinoid metabolism might be a promising strategy in future cancer treatment.

The interplay between cellular metabolism and immune regulation is central to immune function and disease progression, revealing notable therapeutic opportunities. Upon activation, immune cells undergo metabolic reprogramming to meet heightened demands for energy and biosynthesis, reshaping regulatory networks across epigenomic, transcriptomic, and proteomic layers. Metabolite-derived posttranslational modifications (PTMs) serve as pivotal mechanisms integrating metabolic intermediates with immune signaling pathways. Beyond classical acetylation, diverse nonacetyl PTMs—including lactylation, succinylation, malonylation, palmitoylation, and myristoylation—modify histone and nonhistone proteins, regulating gene expression, protein stability, subcellular localization, enzymatic activity, and protein-protein interactions. Advances in mass spectrometry and bioinformatics now enable precise characterization of these PTMs, uncovering their broad roles in immune regulation. This review summarizes current progress in immunometabolism and explores future directions such as mechanistic studies, combination strategies, and clinical applications. Metabolite-driven PTMs critically connect metabolism to immune regulation, suggesting promising therapeutic approaches for cancer, autoimmune disorders, and inflammatory diseases.

RETSAT mediates ferroptosis by activating the retinoic acid receptor pathway.