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Peer-reviewedCC BY 4.0Cells

Membraneless Organelles and Organ Fibrosis: New Perspectives and Therapeutic Opportunities

  • Xikai Liu1
  • Yihao Zhou2
  • Melanie Tran3
  • Yuchen Chen4
  • Dong Yang3
4 affiliations
  1. 1School of Biological and Chemical Engineering, Nanyang Institute of Technology, Nanyang 473004, China
  2. 2College of Life Sciences, Wuhan University, Wuhan 430072, China
  3. 3Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT 06030, USA
  4. 4Division of Surgical Sciences, Department of Surgery, University of Virginia, Charlottesville, VA 22903, USA
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Abstract

Organ fibrosis is a maladaptive repair outcome in which persistent injury drives extracellular matrix (ECM) accumulation, distortion of tissue architecture, and progressive loss of organ function. Although major fibrotic pathways are well established, it remains less clear how mechanical, inflammatory, oxidative, metabolic, and other stress signals are spatially organized and converted into persistent cell-state changes. Many biomolecular condensates, also known as membraneless organelles (MLOs), are organized through liquid–liquid phase separation (LLPS), which can alter signaling efficiency, transcriptional output, RNA handling, and stress responses. Increasing evidence links this mode of molecular organization to fibrosis-relevant pathways across the kidney, liver, cardiovascular system, and lung. In this review, we summarize current evidence for MLO-mediated regulation of organ fibrosis, discuss the potential to therapeutically modulate assembly, client recruitment, and material properties, and highlight key translational challenges, including in vivo causality, cell-type and disease-stage selectivity, delivery, and safety. Overall, MLOs provide a useful framework for understanding how fibrotic signals are organized and sustained, while also opening therapeutic opportunities beyond conventional single-node inhibition.

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Cite

BibTeXRIS
BibTeX
@article{liu2026membraneless,
  title = {{Membraneless Organelles and Organ Fibrosis: New Perspectives and Therapeutic Opportunities}},
  author = {Xikai Liu and Yihao Zhou and Melanie Tran and Yuchen Chen and Dong Yang},
  journal = {Cells},
  year = {2026},
  month = oct,
  doi = {10.3390/cells15201872},
  url = {https://www.mdpi.com/2073-4409/15/20/1872},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Membraneless Organelles and Organ Fibrosis: New Perspectives and Therapeutic Opportunities
AU  - Xikai Liu
AU  - Yihao Zhou
AU  - Melanie Tran
AU  - Yuchen Chen
AU  - Dong Yang
PY  - 2026
DA  - 2026/10/15
JO  - Cells
DO  - 10.3390/cells15201872
UR  - https://www.mdpi.com/2073-4409/15/20/1872
AB  - Organ fibrosis is a maladaptive repair outcome in which persistent injury drives extracellular matrix (ECM) accumulation, distortion of tissue architecture, and progressive loss of organ function. Although major fibrotic pathways are well established, it remains less clear how mechanical, inflammatory, oxidative, metabolic, and other stress signals are spatially organized and converted into persistent cell-state changes. Many biomolecular condensates, also known as membraneless organelles (MLOs), are organized through liquid–liquid phase separation (LLPS), which can alter signaling efficiency, transcriptional output, RNA handling, and stress responses. Increasing evidence links this mode of molecular organization to fibrosis-relevant pathways across the kidney, liver, cardiovascular system, and lung. In this review, we summarize current evidence for MLO-mediated regulation of organ fibrosis, discuss the potential to therapeutically modulate assembly, client recruitment, and material properties, and highlight key translational challenges, including in vivo causality, cell-type and disease-stage selectivity, delivery, and safety. Overall, MLOs provide a useful framework for understanding how fibrotic signals are organized and sustained, while also opening therapeutic opportunities beyond conventional single-node inhibition.
SN  - 2073-4409
ER  -