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

Authors

Alexandra Bermudez, Zoe Latham, Johnny Diaz, Weihong Yan, Jerry Chen, Dapeng Bi, Andrew S Goldstein, Jimmy K Hu, Neil Y C Lin

Published in

Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 41. Pages e2617216123. Oct 13, 2026. Epub Oct 07, 2026.

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.

PMID:
42842400
Bibliographic data and abstract were imported from PubMed on 08 Oct 2026.

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