The succinated proteome

Area of Science:

• Biochemistry
• Cellular Biology
• Proteomics

Background:

• Post-translational modifications (PTMs) like succination alter protein function in response to cellular redox changes.
• Succination involves fumarate modification of cysteine residues, forming S-(2-succino)cysteine (2SC).
• Increased succination correlates with mitochondrial, ER, and oxidative stress in conditions like diabetes and obesity.

Purpose of the Study:

• To review the history and current understanding of the succinated proteome.
• To discuss the challenges in measuring succination using proteomics.
• To highlight succination's role as a biomarker and mechanistic link in chronic diseases.

Main Methods:

• Review of existing literature on protein succination.
• Analysis of proteomic data identifying succinated proteins.
• Correlation of succination levels with cellular stress markers and disease states.

Main Results:

• Succination targets a diverse range of proteins, including enzymes and chaperones.
• Protein succination is elevated in adipose tissue during obesity/diabetes and in specific mouse models.
• Succination is linked to mitochondrial dysfunction, ER stress, and apoptosis, with potential overlap with glutathionylation.

Conclusions:

• S-(2-succino)cysteine (2SC) is a potential biomarker for mitochondrial stress in chronic diseases like diabetes, obesity, and cancer.
• Succination may represent a key mechanism connecting mitochondrial dysfunction to cellular stress and apoptosis.
• Further research is needed to refine proteomics approaches for studying succination.