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Peer-reviewedCC BYProceedings of the National Academy of Sciences of the United States of America

Cell jamming transition is regulated by mitochondrial pyruvate transport and endocytosis.

  • Alexandra Bermudez1,2
  • Zoe Latham2
  • Johnny Diaz3
  • Weihong Yan4
  • Jerry Chen2
  • Dapeng Bi5
  • Andrew S Goldstein3
  • Jimmy K Hu6,7
  • Neil Y C Lin1,2,7
7 affiliations
  1. 1Mechanical and Aerospace Engineering Department, University of California, Los Angeles, CA 90095.
  2. 2Bioengineering Department, University of California, Los Angeles, CA 90095.
  3. 3Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA 90095.
  4. 4Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095.
  5. 5Department of Physics, Northeastern University, Boston, MA 02115.
  6. 6Division of Biosystems and Function, School of Dentistry, University of California, Los Angeles, CA 90095.
  7. 7Broad Stem Cell Center, University of California, Los Angeles, CA 90095.
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Abstract

Epithelial tissues undergo dynamic transitions between fluid-like collective motion and mechanically jammed states during development, injury repair, and disease progression. However, the cellular programs that drive these transitions and regulate collective behavior remain unclear. Using a controlled crowding model integrated with live-cell imaging and time-resolved multiomics, we demonstrate that epithelial crowding triggers early metabolic changes characterized by increased mitochondrial pyruvate anaplerosis that precedes the jamming transition. Restricting mitochondrial pyruvate import increased collective cell motility and delayed jamming in crowded monolayers. This unjammed state is driven by enhanced cytoskeletal remodeling and requires RhoA-myosin II activity. Mechanistically, we show that elevated cytoskeletal signaling promotes macropinocytic uptake, which serves as a required feedback loop to maintain motility. These findings identify mitochondrial pyruvate utilization as an important regulatory input linking metabolic remodeling to the endocytic control of epithelial fluidity.

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Cite

BibTeXRIS
BibTeX
@article{bermudez2026cell,
  title = {{Cell jamming transition is regulated by mitochondrial pyruvate transport and endocytosis.}},
  author = {Alexandra Bermudez and Zoe Latham and Johnny Diaz and Weihong Yan and Jerry Chen and Dapeng Bi and Andrew S Goldstein and Jimmy K Hu and Neil Y C Lin},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  year = {2026},
  month = oct,
  doi = {10.1073/pnas.2617216123},
  url = {https://europepmc.org/article/MED/42842400},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Cell jamming transition is regulated by mitochondrial pyruvate transport and endocytosis.
AU  - Alexandra Bermudez
AU  - Zoe Latham
AU  - Johnny Diaz
AU  - Weihong Yan
AU  - Jerry Chen
AU  - Dapeng Bi
AU  - Andrew S Goldstein
AU  - Jimmy K Hu
AU  - Neil Y C Lin
PY  - 2026
DA  - 2026/10/07
JO  - Proceedings of the National Academy of Sciences of the United States of America
DO  - 10.1073/pnas.2617216123
UR  - https://europepmc.org/article/MED/42842400
AB  - Epithelial tissues undergo dynamic transitions between fluid-like collective motion and mechanically jammed states during development, injury repair, and disease progression. However, the cellular programs that drive these transitions and regulate collective behavior remain unclear. Using a controlled crowding model integrated with live-cell imaging and time-resolved multiomics, we demonstrate that epithelial crowding triggers early metabolic changes characterized by increased mitochondrial pyruvate anaplerosis that precedes the jamming transition. Restricting mitochondrial pyruvate import increased collective cell motility and delayed jamming in crowded monolayers. This unjammed state is driven by enhanced cytoskeletal remodeling and requires RhoA-myosin II activity. Mechanistically, we show that elevated cytoskeletal signaling promotes macropinocytic uptake, which serves as a required feedback loop to maintain motility. These findings identify mitochondrial pyruvate utilization as an important regulatory input linking metabolic remodeling to the endocytic control of epithelial fluidity.
SN  - 0027-8424
SN  - 1091-6490
ER  -