bims-lycede 2026-02-22 papers

Acta Physiol (Oxf). 2026 Mar;242(3): e70160

Lysosome pH Dynamics in Physiology and Disease: Molecular Mechanisms and Therapeutic Insights.

BACKGROUND: An acidic lysosomal lumen (pH ~4.5) is essential for the degradative and signaling functions of this organelle, which serves as a central hub for cellular homeostasis. Lysosome pH (pHlys), however, is not static but dynamically regulated by the coordinated action of the V-ATPase, counterion fluxes, membrane composition, and nutrient-sensitive signaling networks.
PURPOSE: This review integrates recent advances in the molecular mechanisms regulating pHlys with emerging insights on how dysregulated pHlys contributes to pathologies in neurodegenerative disorders, lysosomal storage diseases, and cancers with changes in lumenal proteolytic activity and macromolecular degradation.
MAIN FINDINGS: We discuss how pHlys acts as both a sensor and effector in lysosome biology, shaping transcriptional responses, membrane trafficking, and stress adaptation. We also review tools to measure pHlys, ranging from fluorescent dyes to genetically encoded biosensors and nanomaterial-based probes, and evaluate their use in disease-modeling applications.
CONCLUSIONS: By highlighting pHlys as a nodal point in cellular functions, this review underscores the relevance of pHlys as a diagnostic marker and therapeutic target. Restoring pHlys in diseases offers translational potential to re-establish proteostasis and limit associated pathologies.

Keywords: cancer; lysosomal signaling; lysosome pH; neurodegeneration; pHlys regulation

DOI: https://doi.org/10.1111/apha.70160

Subcell Biochem. 2026 ;111 331-350

Golgi Membrane-Associated Degradation (GOMED), a New Intracellular Proteolysis Mechanism.

Shigeomi Shimizu, Shinya Honda, Satoru Torii, Satoko Arakawa, Masatsune Tsujioka, Hirofumi Yamaguchi, Hajime Tajima Sakurai.

The Golgi apparatus is a crucial organelle that is involved in various cellular processes, including cellular secretion, and is primarily responsible for the modification, sorting, and transport of proteins and lipids. However, recently, we discovered a novel Golgi function, namely, Golgi membrane-associated degradation (GOMED). GOMED is a cellular function in which the trans-Golgi membrane undergoes deformation and becomes spherical, breaking down proteins and lipids that have been internalized. This process is conserved from yeast to mammalian cells. GOMED primarily plays a role in the quality control of hormones, cytokines, and cell membrane receptors that pass through the Golgi apparatus, and is crucial for maintaining the normal function of pancreatic β cell, neurons, and intestinal epithelial cells. Therefore, abnormalities in GOMED can lead to neurodegenerative diseases and inflammatory bowel diseases.

Keywords: Autophagy; GOMED; Golgi apparatus; ULK1; Wipi3

DOI: https://doi.org/10.1007/978-3-032-16833-7_14

Subcell Biochem. 2026 ;111 133-176

COG Complex in Golgi Trafficking and Glycosylation.

Farhana Taher Sumya, Vladimir V Lupashin.

The Conserved Oligomeric Golgi (COG) complex, an evolutionary conserved octameric vesicular tether, is essential for maintaining Golgi function by ensuring accurate delivery of resident proteins to their specific locations. Mutations in human COG subunits result in severe multi-systemic diseases known as COG-Congenital Disorders of Glycosylation (COG-CDG). This review explores the current knowledge of COG complex structure, its dynamic behavior, interactions with partner proteins, and proposed models of its cellular functions. Furthermore, we will discuss the pathological implications of mutations in COG complex subunits, as observed in model organisms and human patients.

Keywords: Congenital disorders of glycosylation; Golgi; SNARE; Vesicle tethering; COG

DOI: https://doi.org/10.1007/978-3-032-16833-7_7

Subcell Biochem. 2026 ;111 251-267

Regulation of Glycan Modification by Glycosyltransferases in the Golgi Apparatus.

Hirokazu Yagi, Seigo Tateo, Koichi Kato.

Protein glycosylation, a fundamental modification critical for diverse biological functions, is well orchestrated within the Golgi apparatus, a central organelle in the secretory pathway. This review explores the mechanisms by which the Golgi governs protein-specific glycan modification, emphasizing the spatial organization of glycosyltransferases within the Golgi and the regulated transport of glycoproteins through its compartments. Specificity arises from the strategic localization of glycosyltransferases within the Golgi, enabling them to recognize both glycan structures and protein domains on their substrates. Advanced imaging reveals a complex and dynamic organization within the Golgi, challenging traditional models and highlighting specialized zones. Regulated transport of glycoproteins through the Golgi is critical for controlling their access to modifying enzymes. Specific sequence motifs within glycoproteins can act as 'passport sequence', directing them to distinct Golgi regions and influencing glycosylation by altering their proximity to specific enzymes and accessory proteins. These mechanisms support the hypothesis that sequence-dependent signals within substrate proteins influence their trafficking, enabling precise glycosylation as they transit the Golgi. Understanding these processes provides new insights into how glycan diversity is generated and regulated within the Golgi, highlighting the interplay between enzyme localization, protein trafficking, and the dynamic organization of this essential organelle.

Keywords: Glycoprotein; Glycosylation; Glycosyltransferase; Golgi apparatus; Protein-specific glycan modification; Substrate recognition

DOI: https://doi.org/10.1007/978-3-032-16833-7_11

Front Mol Neurosci. 2026 ;19 1755292

Lysosome trafficking across intracellular and intercellular networks in the brain.

Dylan T Murphy, Chih Hung Lo.

Keywords: cell-cell interaction; intrinsically disordered proteins (IDPs); lysosome acidification; lysosome trafficking; microtubule transport; neurodegenerative diseases; neuron-glia communication; tunneling nanotubes (TNTs)

DOI: https://doi.org/10.3389/fnmol.2026.1755292