Publication in Nature Cell Biology 2019 volume 21 pages 338–347
Extracellular matrix mechanical cues regulate lipid metabolism through Lipin-1 and SREBP
Patrizia Romani, Irene Brian, Giulia Santinon, Arianna Pocaterra, Matteo Audano, Silvia Pedretti, Samuel Mathieu, Mattia Forcato, Silvio Bicciato, Jean-Baptiste Manneville, Nico Mitro and Sirio Dupont Nature Cell Biology volume 21, pages338–347 (2019), doi: 10.1038/s41556-018-0270-5
Extracellular matrix (ECM) mechanical cues have powerful effects on cell proliferation, differentiation and death. Here, starting from an unbiased metabolomics approach, we identify synthesis of neutral lipids as a general response to mechanical signals delivered by cell–matrix adhesions. Extracellular physical cues reverberate on the mechanical properties of the Golgi apparatus and regulate the Lipin-1 phosphatidate phosphatase. Conditions of reduced actomyosin contractility lead to inhibition of Lipin-1, accumulation of SCAP/SREBP to the Golgi apparatus and activation of SREBP transcription factors, in turn driving lipid synthesis and accumulation. This occurs independently of YAP/TAZ, mTOR and AMPK, and in parallel to feedback control by sterols. Regulation of SREBP can be observed in a stiffened diseased tissue, and contributes to the pro-survival activity of ROCK inhibitors in pluripotent stem cells. We thus identify a general mechanism centered on Lipin-1 and SREBP that links the physical cell microenvironment to a key metabolic pathway.
See “News and Views” – Golgi mechanics controls lipid metabolism (doi:10.1038/s41556-019-0289-2)