The pyrin inflammasome senses OCTN2-mediated uptake of extracellular ʟ-carnitine from muscle injury or ingestion.

Authors

Eric I Elliott, Tomomi M Yoshida, Susana C B R Nakandakari, Scott Pope, Cuiling Zhang, Timothy Nottoli, Jae Jin Chae, Daniel L Kastner, Richard A Flavell, Vishwa Deep Dixit, Vijay A Rathinam, Fayyaz S Sutterwala, Andrew Wang

Published in

Cell. Oct 19, 2026. Epub Oct 19, 2026.

Abstract

Red-meat-containing diets are epidemiologically associated with diseases of chronic inflammation, while diets that restrict red meat improve health. Yet, it is uncertain how red meat incites inflammation. Here, we discover that ʟ-carnitine, an amino acid highly concentrated in skeletal muscle myocytes, drives inflammasome activation in lipopolysaccharide (LPS)-challenged mice and LPS-primed murine and human macrophages. We find that extracellular ʟ-carnitine represses mevalonate synthesis, thereby triggering activation of the pyrin inflammasome, downstream of cellular import by the high-affinity ʟ-carnitine transporter OCTN2. We find that the inflammatory response to skeletal muscle injury also requires pyrin and OCTN2. Thus, in summary, we identify macrophages as sentinels of exogenous and endogenous extracellular ʟ-carnitine that serve as a proxy for skeletal myocyte damage, and we open the field to examine the mechanistic basis for how excess dietary intake of carnitine-rich food drives inflammatory disease.

PMID:
42896553
Bibliographic data and abstract were imported from PubMed on 20 Oct 2026.

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