Endomembranes: Unsung Heroes of Mechanobiology?

Abstract

Mechanical stimuli have profound effects on the cellular architecture and functions. Over the past two decades, considerable progress has been made in unraveling the molecular machineries that confer cells the ability to sense and transduce mechanical input into biochemical signals. This has resulted in the identification of several forcesensing proteins or mechanically activated ion channels distributed throughout most cell types, whereby the plasma membrane, cytoskeleton, and the nucleus have garnered much attention. Although organelles from the endomembrane system make up significant portion of cell volume and play pivotal roles in the spatiotemporal distribution of signaling molecules, they have received surprisingly little attention in mechanobiology. In this mini-review, we summarize results that document participation of the endomembrane system in sensing and responding to mechanical cues.

Mitochondria: At the crossroads between mechanobiology and cell metabolism

“…However, how external forces are transmitted from the plasma membrane to mitochondria is still largely unexplored. As for other endomembranes (Phuyal & Baschieri, 2020) and for the nucleus, the cytoskeleton is probably a major actor. Several studies have shown that external mechanical stimulation of either intracellular or isolated mitochondria increase fission or fusion events (Phuyal et al, 2023).…”

“…Cells sense and process signals from their external environment to coordinate structural and functional processes such as growth, proliferation, homeostasis and compressive, tensile or shear stresses are transmitted into the cell through the coordinated activity of mechanosensors along mechanosignaling pathways. Previous studies have investigated and reviewed the role of the plasma membrane, mechano-activated ion channels, focal adhesion proteins, cytoskeletal filaments (actin, microtubule and intermediate filaments) and the nucleus in sensing and transducing mechanical stresses (Ingber, 2006;Orr et al, 2006;Jaalouk & Lammerding, 2009;Schwartz, 2010;Isermann & Lammerding, 2013;Douguet & Honoré, 2019;Kechagia et al, 2019;Uray & Uray, 2021), but the molecular mechanisms of mechanotransduction are still incompletely understood, in particular when intracellular compartments such as the endomembrane system are involved (Phuyal & Baschieri, 2020;Phuyal et al, 2023). With the spurring growth of intracellular rheology, the mechanical properties of the cytoplasm, intracellular organelles and the cytoskeleton emerge as key players in both mechanosensing and mechanotransduction (Mathieu & Manneville, 2019).…”

Morphological Heterogeneity of the Endoplasmic Reticulum within Neurons and Its Implications in Neurodegeneration

“…The complex structure of the ER is also highly dynamic and changes according to the cell’s requirements. What regulates the changes is still not fully understood, but the ER network is constantly rearranging and redistributing, aided by multiple factors [ 33 , 34 , 35 ] and has even been found to be sensitive to mechanical stimuli [ 36 ].…”

Mechanical strain stimulates COPII‐dependent secretory trafficking via Rac1

“…It is now well established that such mechanical cues trigger signaling pathways that mediate changes in cell differentiation, proliferation, growth, and survival (Engler et al , 2006 ; Roca‐Cusachs et al , 2013 ; Gudipaty et al , 2017 ; Janmey et al , 2020 ). Most research in the area of mechanobiology has focused on the plasma membrane, the nucleus, or the cytoskeleton as receivers and mediators of mechanical signaling (Phuyal & Baschieri, 2020 ). However, it is currently poorly understood whether and how mechanical stress has any effect on early secretory pathway compartments such as ERES.…”