Itaconate modifications: Mechanisms and applications

Area of Science:

• Immunometabolism
• Biochemistry
• Molecular Biology

Background:

• Itaconate is a mitochondrial metabolite derived from cis-aconitate via aconitate decarboxylase 1 (ACOD1).
• Itaconate and its derivatives regulate immune and inflammatory signaling through post-translational modifications.
• These modifications impact key immune regulators and cellular pathways like inflammation, oxidative stress, and cell death.

Purpose of the Study:

• To review the biosynthesis, molecular targets, and post-translational modifications of itaconate.
• To explore the therapeutic potential of itaconate derivatives in preclinical models.
• To underscore itaconate's role in immunometabolic reprogramming and inflammatory control.

Main Methods:

• Literature review integrating current insights on itaconate.
• Analysis of preclinical studies on itaconate derivatives.
• Discussion of itaconate's biosynthesis, targets, modifications, detection, and translational potential.

Main Results:

• Itaconate modulates cellular processes via S-itaconation and K-itaconation.
• Itaconate derivatives demonstrate therapeutic benefits in sepsis, colitis, neurodegeneration, autoimmunity, and cancer.
• Endogenous itaconate has context-dependent pro-resolving or immunostimulatory effects.

Conclusions:

• Itaconate is a critical regulator of immunometabolic reprogramming.
• Itaconate derivatives hold significant therapeutic promise.
• Further research into itaconate's mechanisms can advance inflammatory disease treatment.