Physical constraints, such as compression, shear stress, stretching and tension, play major roles during development, tissue homeostasis, immune responses and pathologies. Cells and organelles also face mechanical forces during migration and extravasation, and investigations into how mechanical forces are translated into a wide panel of biological responses, including changes in cell morphology, membrane transport, metabolism, energy production and gene expression, is a flourishing field. Recent studies demonstrate the role of macroautophagy in the integration of physical constraints. The aim of this Review is to summarize and discuss our knowledge of the role of macroautophagy in controlling a large panel of cell responses, from morphological and metabolic changes, to inflammation and senescence, for the integration of mechanical forces. Moreover, wherever possible, we also discuss the cell surface molecules and structures that sense mechanical forces upstream of macroautophagy.

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