Organelle regulation of SUMOylation: regulatory mechanisms and therapeutic application

Abstract

Background: SUMOylation is a pivotal post-translational modification (PTM) that has been extensively investigated in nuclear processes. However, its role in regulating suborganelle homeostasis warrants further exploration. Recent studies have highlighted the significance of SUMOylation in modulating mitochondrial dynamics and endoplasmic reticulum stress (ERS), among other cellular processes, thereby offering novel insights into disease pathogenesis.

Aim of review: This review aims to systematically elucidate the roles and mechanisms of SUMOylation in regulating the homeostasis of various organelles. Furthermore, it integrates emerging evidence concerning the regulation of multi-organelle functions via SUMOylation and its associated PTM network. Additionally, it proposes novel therapeutic strategies targeting the SUMOylation pathway for diseases linked to these processes.

Key scientific concepts of review: SUMOylation plays a pivotal role in regulating fundamental cellular processes, including mitochondrial function, ER protein folding, intracellular vesicle transport and degradation, ribosome assembly, and lipid droplet formation. By serving as a bridge for inter-organelle signal communication, SUMOylation coordinates cross-organelle stress responses and acts as a central regulatory hub for maintaining organelle homeostasis. Moreover, the intricate network formed by SUMOylation in conjunction with other PTMs, such as ubiquitination and phosphorylation, collaboratively regulates organelle states and functions as a critical molecular switch for controlling cellular protein homeostasis. Currently, targeted intervention strategies focusing on the SUMOylation pathway have emerged as a promising translational medicine research direction for restoring organelle homeostasis and addressing tumors and metabolic diseases, demonstrating broad clinical application potential.

Keywords: ERS; Mitochondrial homeostasis; Organelle-specific regulation; PTM; SUMOylation.