Work

SUMOylation and deSUMOylation in sepsis-associated organ injury: cellular mechanisms and translational challenges

Year: 2026

Type: article

Abstract: Small ubiquitin-like modifier (SUMO) conjugation (SUMOylation) and deconjugation (deSUMOylation) regulate protein stability, subcellular localisation, and protein interactions, but their contributions to organ injury in sepsis remain incompletely understood. This review assesses SUMO-related evidence according to disease relevance and mechanistic causality, distinguishing findings from patient samples and infection-based sepsis models from those obtained in endotoxemia, acute injury models, and other nonsepsis systems. Available evidence implicates SUMOylation and deSUMOylation in inflammatory signalling, immunometabolic adaptation, barrier homeostasis, mitochondrial quality control, and regulated cell death, suggesting potential links between immune dysfunction, cellular stress, and organ injury. Their effects depend on the SUMO paralogue, regulatory enzyme, substrate, modification site, cell type, tissue compartment, and infection context. Changes in bulk SUMO1 or SUMO2/3 conjugation therefore cannot be interpreted as uniformly protective or pathogenic. Direct human evidence and causal evidence resolved by cell type in infection-based models remain limited, and many proposed mechanisms lack endogenous site mapping or rescue validation. Broad pharmacological inhibition of the SUMO pathway has produced discordant results across experimental models, and the clinical safety and efficacy of interventions targeting SUMO in sepsis remain unestablished. Future studies should establish causal relationships between SUMO enzymes, substrates, and modification sites in defined cell types; develop reproducible pharmacodynamic biomarkers; and evaluate targeted interventions in clinically relevant models after infection is established.

Source: Cell Biology and Toxicology

DOI: 10.1007/s10565-026-10307-8

Authors: Lihong Yang, Fajuan Tang, Xiuming Hu, Lingli Pan, Dongqiong Xiao

Institutions: Sichuan University, West China Second University Hospital of Sichuan University

Language: English

Topic: Ubiquitin and proteasome pathways

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,190