How Do Succinylation Antibodies Reveal the Key Role of Protein Modification in Disease Pathogenesis?

I. What is the Biological Significance of Protein Succinylation?

Protein succinylation, as an important post-translational modification, refers to the biochemical process where a succinyl group is covalently attached to a lysine residue of a substrate protein via enzymatic catalysis or non-enzymatic reactions in the presence of donors like succinyl-CoA. This modification is widely involved in regulating core energy metabolism pathways such as the tricarboxylic acid cycle and glucose metabolism, playing a crucial role in maintaining cellular energy homeostasis. Recent research has found that succinylation is closely associated with various pathological states, including tumorigenesis, neurodegenerative diseases, metabolic disorders, and inflammatory responses, by affecting fundamental biological processes like mitochondrial function, gene expression regulation, and signal transduction.

The dynamic balance of succinylation is co-regulated by succinyltransferases and desuccinylases. SIRT5, as a major desuccinylase, plays a central role in maintaining this balance. Advances in proteomics technologies have revealed that aberrant succinylation is directly linked to the development and progression of various human diseases, making research targeting succinylation a hotspot in current biomedicine. Succinylation antibodies, as key tools for detecting this modification, provide essential technical support for in-depth exploration of its biological functions.

II. How Does Succinylation Regulate Tumor Metabolism and Therapy Resistance?

In papillary thyroid carcinoma research, scientists discovered that the long non-coding RNA GLTC promotes tumor progression and therapy resistance by regulating the succinylation of lactate dehydrogenase A (LDHA). GLTC is significantly overexpressed in papillary thyroid carcinoma tissues and is closely associated with distant metastasis, increased tumor volume, and poor prognosis. Mechanistic studies show that GLTC, acting as an LDHA binding partner, competitively inhibits the interaction between SIRT5 and LDHA, promoting LDHA succinylation at the K155 site and thereby enhancing its enzymatic activity.

This modification leads to enhanced aerobic glycolysis and increased cell viability in tumor cells, consequently promoting malignant progression. Importantly, expressing the succinylation-mimetic mutant LDHAK155E can restore the glycolysis and cell viability impaired by GLTC knockdown. The study also found that GLTC influences tumor sensitivity to radioactive iodine therapy by regulating LDHA succinylation, suggesting that targeting the GLTC-LDHA succinylation axis could be a novel strategy to overcome therapy resistance. These findings not only reveal the critical role of succinylation in tumor metabolic reprogramming but also provide a theoretical basis for developing new therapeutic targets.

III. How Does Desuccinylation Maintain Cellular Homeostasis and Delay Disease Progression?

In intervertebral disc degeneration research, SIRT5-mediated desuccinylation has been shown to play a key role in maintaining mitochondrial homeostasis. The study found that SIRT5 expression is significantly reduced in rat nucleus pulposus tissue under mechanical stress, leading to impaired mitochondrial function and increased apoptosis. Through four-dimensional label-free quantitative proteomic analysis, researchers identified apoptosis-inducing factor mitochondria-associated 1 (AIFM1) as a key substrate of SIRT5. Decreased SIRT5 expression causes elevated AIFM1 succinylation, which disrupts the AIFM1-CHCHD4 interaction, resulting in reduced electron transport chain complex subunits and mitochondrial dysfunction.

In animal models, SIRT5 knockout mice exhibited more severe intervertebral disc degeneration phenotypes after lumbar spine destabilization surgery, whereas SIRT5 overexpression or methylene blue treatment effectively alleviated mechanical stress-induced mitochondrial damage and disc degeneration progression. This research not only clarifies the molecular mechanism of the SIRT5-AIFM1 axis in disc degeneration but also provides new insights for developing therapeutic strategies targeting protein desuccinylation.

IV. How Does Succinylation Affect Transcriptional Regulation and Tumorigenesis?

In lung adenocarcinoma research, the p23 co-chaperone was identified as a novel succinate-activated COX-2 transcription factor. The study found that nuclear localization of p23 is closely associated with poor patient prognosis, and the accumulation of succinate in tumor cells promotes p23 succinylation at K7, K33, and K79 sites, driving its nuclear translocation, activating COX-2 transcription, and consequently promoting tumor growth. This discovery reveals a new mechanism for p23's function independent of heat shock protein 90.

Through large-scale virtual screening and biological validation, researchers identified the small molecule compound M16, which effectively inhibits p23 succinylation, blocks its nuclear translocation and COX-2 transcriptional activation, thereby significantly suppressing tumor growth. This study not only defines p23 as a succinate-activated transcription factor for the first time but also provides a new theoretical basis and candidate compound for developing anti-cancer drugs targeting protein succinylation.

V. What is the Application Prospect and Development Direction of Succinylation Antibodies?

Future research directions should include developing succinylation antibodies with higher specificity and sensitivity, establishing standardized detection protocols, and exploring specific patterns of succinylation modification in different disease contexts. Simultaneously, integrating multi-omics technologies and artificial intelligence analysis methods to comprehensively decipher the regulatory mechanisms of the succinylation modification network will drive this field towards deeper development. As a crucial bridge connecting basic discoveries and clinical applications, succinylation antibodies will undoubtedly play an increasingly important role in disease mechanism research and drug development.

VI. Which Manufacturers Provide Succinylation Antibodies?

Hangzhou Start Bio-tech Co., Ltd.'s self-developed "Succinyllysine Rabbit Polyclonal Antibody" is a metabolic modification research tool characterized by high modification specificity, broad-spectrum recognition capability, and excellent affinity. This product is ideal for cutting-edge research in metabolism and epigenetics, enzyme function regulation, and disease mechanism exploration.

Product Core Advantages:

• High Modification Specificity & Broad-Spectrum Recognition: Cross-validated with modified/unmodified peptides, it precisely recognizes succinylation modifications occurring on lysine residues, with almost no cross-reactivity to other common acylations (e.g., acetylation, crotonylation). Its polyclonal nature enables recognition of succinylation across different protein backgrounds, offering wide coverage.
• Excellent Affinity & Inter-batch Stability: The product exhibits high affinity, effectively enriching and detecting endogenously succinylated proteins. Strict serum pool management and purification processes ensure high performance consistency across different batches, providing reliable support for long-term research projects.

Suitable Key Application Scenarios:
This product is an ideal tool for conducting the following research:

• Metabolite Sensing & Signal Transduction Research: For exploring how metabolites like succinyl-CoA regulate cellular function by inducing protein succinylation, linking cellular metabolic state to protein function.
• Metabolic Enzyme Activity Regulation Research: For studying the precise regulatory mechanisms of succinylation on the activity of various metabolic enzymes (e.g., enzymes involved in the TCA cycle, fatty acid oxidation).
• Mitochondrial Function & Metabolic Disease Research: For investigating the role of succinylation of mitochondrial proteins in energy metabolism, oxidative stress, and the pathogenesis of metabolic diseases (e.g., diabetes, obesity).
• Epigenetics & Gene Expression Regulation: For identifying succinylation sites on histones and studying their novel functions in transcriptional regulation and chromatin dynamics.

Professional Technical Support: We provide detailed product technical documentation, including specificity validation data, experimental protocols for various application platforms, a recommended target list, and professional technical consultation, fully committed to assisting customers in achieving leading discoveries in the rapidly evolving field of metabolic modification research.

Hangzhou Start Bio-tech Co., Ltd. is always dedicated to providing high-quality, high-value biological reagents and solutions for global innovative pharmaceutical companies and research institutions. For more details about the "Succinyllysine Rabbit Polyclonal Antibody" or to request a sample test, please feel free to contact us.

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