Misregulation of the Ubiquitin–Proteasome System and Autophagy in Muscular Dystrophies Associated with the Dystrophin–Glycoprotein Complex DOI Creative Commons
Manuela Bozzi, Francesca Sciandra, Maria Giulia Bigotti

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(10), P. 721 - 721

Published: May 15, 2025

The stability of the sarcolemma is severely impaired in a series genetic neuromuscular diseases defined as muscular dystrophies. These are characterized by centralization skeletal muscle syncytial nuclei, replacement fibers with fibrotic tissue, release inflammatory cytokines, and disruption protein homeostasis, ultimately leading to necrosis loss functionality. A specific subgroup dystrophies associated defects components dystrophin-glycoprotein complex (DGC), which plays crucial role linking cytosol basement membrane. In these cases, dystrophin-associated proteins fail correctly localize sarcolemma, resulting dystrophy an uncontrolled increase degradation, can lead cell death. this review, we explore intracellular degradative pathways-primarily ubiquitin-proteasome autophagy-lysosome systems-in progression DGC-linked DGC acts hub for numerous signaling pathways that regulate various cellular functions, including homeostasis. We examine whether structural within affects key modulate recycling, particular emphasis on autophagy.

Language: Английский

Lysosomal degradation of ER client proteins by ER-phagy and related pathways DOI Creative Commons
Carla Salomo-Coll, Natalia Jiménez-Moreno, Simon Wilkinson

et al.

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169035 - 169035

Published: Feb. 1, 2025

The endoplasmic reticulum (ER) is a major site of cellular protein synthesis. Degradation overabundant, misfolded, aggregating or unwanted proteins required to maintain proteostasis and avoid the deleterious consequences aberrant accumulation, at organismal level. While extensive research has shown an important role for proteasomally-mediated, ER-associated degradation (ERAD) in maintaining proteostasis, it becoming clear that there substantial lysosomal "client" from ER lumen membrane (ER-to-lysosome degradation, ERLAD). Here we provide brief overview broad categories ERLAD - predominantly ER-phagy (ER autophagy) pathways related processes. We collate client known date, either individual species proteins. Where known, summarise molecular mechanisms by which they are selected setting client(s) correct cell tissue function. Finally, highlight questions remain open this area.

Language: Английский

Citations

1
Autophagy, ER-phagy and ER dynamics during cell differentiation DOI Creative Commons
Michele Cillo,

Viviana Buonomo,

Anna Vainshtein

et al.

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169151 - 169151

Published: April 1, 2025

The endoplasmic reticulum (ER) is a multifunctional organelle essential for protein and lipid synthesis, ion transport inter-organelle communication. It comprises highly dynamic network of membranes that continuously reshape to support wide range cellular processes. During differentiation, extensive remodelling both ER architecture its proteome required accommodate alterations in cell morphology function. Autophagy, ER-phagy particular, plays pivotal role reshaping the ER, enabling cells meet their evolving needs adapt developmental cues. Despite ER's critical mechanisms responsible regulating dynamics are not fully understood. Emerging evidence suggests transcriptional post-translational regulation play fine-tuning unfolded response (UPR). This review explores molecular basis autophagy ER-phagy, highlighting during differentiation. A deeper understanding these processes could open new avenues targeted therapeutic approaches conditions where impaired.

Language: Английский

Citations

0
A RETREG1/FAM134B isoform switch regulates reticulophagy during myogenesis DOI Creative Commons

Viviana Buonomo,

Michele Cillo, Paolo Grumati

et al.

Autophagy, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 3

Published: April 25, 2025

During skeletal muscle development, the sarcoplasmic reticulum forms through homotypic fusion of ER membranes from individual myoblasts. This involves significant remodeling, characterized by an overhaul its proteomic landscape and activation reticulophagy. We described how RETREG1/FAM134B is implicated in both shaping morphology degrading Following myoblast differentiation, classic RETREG1/FAM134B1 undergoes lysosomal degradation progressively replaced shorter RETREG1/FAM134B2 isoform. a truncated variant maintaining identical C-terminal region, including functional LIR, but with partial loss reticulon homology domain. The switch between these two isoforms plays crucial role development. Re-expressing Retreg1/Fam134b2 retreg1/fam134b-knockout myoblasts necessary sufficient to rescue abnormal prevent dilation. Conversely, re-expression Retreg1/Fam134b1 only partially rescues defects. highlighted reticulophagy proper dynamics during myogenesis.

Language: Английский

Citations

0
Misregulation of the Ubiquitin–Proteasome System and Autophagy in Muscular Dystrophies Associated with the Dystrophin–Glycoprotein Complex DOI Creative Commons
Manuela Bozzi, Francesca Sciandra, Maria Giulia Bigotti

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(10), P. 721 - 721

Published: May 15, 2025

The stability of the sarcolemma is severely impaired in a series genetic neuromuscular diseases defined as muscular dystrophies. These are characterized by centralization skeletal muscle syncytial nuclei, replacement fibers with fibrotic tissue, release inflammatory cytokines, and disruption protein homeostasis, ultimately leading to necrosis loss functionality. A specific subgroup dystrophies associated defects components dystrophin-glycoprotein complex (DGC), which plays crucial role linking cytosol basement membrane. In these cases, dystrophin-associated proteins fail correctly localize sarcolemma, resulting dystrophy an uncontrolled increase degradation, can lead cell death. this review, we explore intracellular degradative pathways-primarily ubiquitin-proteasome autophagy-lysosome systems-in progression DGC-linked DGC acts hub for numerous signaling pathways that regulate various cellular functions, including homeostasis. We examine whether structural within affects key modulate recycling, particular emphasis on autophagy.

Language: Английский

Citations

0