The cardiac acetyl-lysine proteome.

Area of Science:

• Biochemistry
• Proteomics
• Cardiovascular Research

Background:

• Lysine acetylation is a vital post-translational modification influencing cellular processes.
• Its role in cardiac function, including pathological remodeling and cardioprotection, is increasingly recognized.

Purpose of the Study:

• To comprehensively investigate the role of lysine acetylation in the heart using a proteomic approach.
• To identify novel cardiac acetylated proteins and their functions.

Main Methods:

• Proteomic analysis of guinea pig hearts fractionated into myofilament-, mitochondrial-, and cytosol-enriched components.
• Affinity enrichment of acetylated peptides followed by LC-MS/MS analysis.
• Validation of identified targets using anti-acetyl-lysine immunoblotting.

Main Results:

• Identified 1075 acetylated peptides, 994 acetylation sites, and 240 proteins.
• Mitochondrial targets constituted 59% of proteins and 64% of sites, primarily involved in metabolism and energy production.
• Newly identified targets include Ca(2+)-handling proteins (RyR2, SERCA2) and myofilament proteins (myosin, troponin).

Conclusions:

• Cardiac lysine acetylation significantly impacts substrate selection, bioenergetic performance, and redox balance.
• Newly identified acetylation sites suggest novel mechanisms modulating cardiac excitation-contraction coupling.