Potential for pathogenic protein acylation in succinate dehydrogenase-deficient pheochromocytoma and paraganglioma.
- 1Department of Biochemistry and Molecular Biology, Mayo Clinic , Rochester, Minnesota, USA.
- 2Medical Scientist Training Program, Mayo Clinic Graduate School of Biomedical Sciences and Mayo Clinic Alix School of Medicine, Mayo Clinic , Rochester, Minnesota, USA.
Abstract
Historically, the study of cellular metabolism and the cellular proteome have largely focused on specific proteins and metabolites in certain cellular pathways. With the advent of new 'omics' technologies, researchers have been able to probe disruptions and alterations in cellular homeostasis on a near proteome-wide and metabolome-wide basis. Yet, the truly interconnected and interdependent nature of the cellular metabolome and proteome has only become more evident with the discovery of proteome-wide protein post-translational modifications (PTMs), such as lysine acylation by acetyl-CoA or succinyl-CoA. Such PTMs link proteome function to fluctuating concentrations of tricarboxylic acid (TCA) cycle metabolites. Tumorigenesis in TCA cycle-defective tumors that upregulate acylating agents, such as succinyl-CoA and acetyl-CoA, provides a relevant context for understanding the breadth of protein acylation in disease. In particular, succinate dehydrogenase (SDH)-loss chromaffin cells can be transformed into the neuroendocrine tumors pheochromocytomas and paragangliomas (PPGLs), but sensitive diagnostic and effective therapeutic options for metastatic disease remain limited. Interrogating cell models of SDH-loss PPGLs provides a unique opportunity to capture the effects of SDH loss on cellular metabolism and protein acylation while exploring new avenues for improved diagnostics and novel therapeutic targets in these rare diseases.
Related
- Real-world optimization of cutoff values for enzyme immunoassay-based plasma-free fractionated metanephrines for the diagnosis of pheochromocytoma and paraganglioma: a multicenter retrospective study
- Radiolabelled somatostatin receptor antagonist versus agonist for peptide receptor radionuclide therapy in patients with metastatic pheochromocytoma or paraganglioma: a retrospective pilot study
- Axitinib in Progressive Metastatic Pheochromocytoma and Paraganglioma: Results of a Phase II Study
- Lanreotide for Advanced Pheochromocytoma and Paraganglioma: Results of a Multicenter Phase II Trial
- Advances in Novel Protein Acylation in Urothelial Carcinoma: Research Progress and Biomarker Potential
BibTeX
@article{zhou2026potential,
title = {{Potential for pathogenic protein acylation in succinate dehydrogenase-deficient pheochromocytoma and paraganglioma.}},
author = {Sherry X Zhou and L James Maher},
journal = {Endocrine-related cancer},
year = {2026},
month = oct,
doi = {10.1530/erc-26-0243},
url = {https://europepmc.org/article/MED/42847134},
note = {CC BY},
}
RIS
TY - JOUR
TI - Potential for pathogenic protein acylation in succinate dehydrogenase-deficient pheochromocytoma and paraganglioma.
AU - Sherry X Zhou
AU - L James Maher
PY - 2026
DA - 2026/10/01
JO - Endocrine-related cancer
DO - 10.1530/erc-26-0243
UR - https://europepmc.org/article/MED/42847134
AB - Historically, the study of cellular metabolism and the cellular proteome have largely focused on specific proteins and metabolites in certain cellular pathways. With the advent of new 'omics' technologies, researchers have been able to probe disruptions and alterations in cellular homeostasis on a near proteome-wide and metabolome-wide basis. Yet, the truly interconnected and interdependent nature of the cellular metabolome and proteome has only become more evident with the discovery of proteome-wide protein post-translational modifications (PTMs), such as lysine acylation by acetyl-CoA or succinyl-CoA. Such PTMs link proteome function to fluctuating concentrations of tricarboxylic acid (TCA) cycle metabolites. Tumorigenesis in TCA cycle-defective tumors that upregulate acylating agents, such as succinyl-CoA and acetyl-CoA, provides a relevant context for understanding the breadth of protein acylation in disease. In particular, succinate dehydrogenase (SDH)-loss chromaffin cells can be transformed into the neuroendocrine tumors pheochromocytomas and paragangliomas (PPGLs), but sensitive diagnostic and effective therapeutic options for metastatic disease remain limited. Interrogating cell models of SDH-loss PPGLs provides a unique opportunity to capture the effects of SDH loss on cellular metabolism and protein acylation while exploring new avenues for improved diagnostics and novel therapeutic targets in these rare diseases.
SN - 1351-0088
SN - 1479-6821
ER -