Work

Potential for pathogenic protein acylation in succinate dehydrogenase-deficient pheochromocytoma and paraganglioma

Year: 2026

Type: review

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.

Source: Endocrine Related Cancer

DOI: 10.1530/erc-26-0243

Authors: Sherry X Zhou, L James Maher

Institution: Mayo Clinic

Language: English

Topic: Adrenal and Paraganglionic Tumors

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funders: Paradifference foundation, National Institutes of Health, National Institute of General Medical Sciences