Carmona, BrunoDelgado, Inês L. S.Nolasco, SofiaMarques, RitaGonçalves, JoãoSoares, HelenaHalasa, M.Wawruszak, A.2025-08-292025-08-292025-07Carmona B, Delgado IL, Nolasco S, Marques R, Gonçalves J, Soares H. Tubulin acetylation and the cellular mechanosensing and stress response. In: Halasa M, Wawruszak A, editors. Histone and non-histone reversible acetylation in development, aging and disease. Cham: Springer; 2025. p. 141-62.9783031914591http://hdl.handle.net/10400.21/22060This work was funded by Instituto Politécnico de Lisboa - IPL/IDI&CA2024/HyperCil_ESTeSL and IPL/IDI&CA2024/ENIGMA_ESTeSL -, and also Centro de Química Estrutural is a Research Unit funded by FCT through projects UIDB/00100/2020, and UIDP/00100/2020. Institute of Molecular Sciences is an Associate Laboratory funded by FCT through project LA/P/0056/2020.Microtubule (MT) acetylation has emerged as a critical regulator of cellular stress responses, integrating mechanical and oxidative stimuli to support cellular adaptability and survival. This post-translational modification (PTM) enhances MT flexibility and resilience, enabling cells to withstand mechanical challenges such as changes in extracellular matrix stiffness and applied forces. Through its impact on MT physical properties, acetylation minimizes cytoskeletal breakage, reducing the need for constant remodeling and supporting cellular integrity under mechanical stress. Furthermore, tubulin acetylation regulates intracellular trafficking by modulating interactions with molecular motors, allowing for efficient cargo transport and precise spatial organization without disrupting the MT network. In the context of oxidative stress, tubulin acetylation responds to redox imbalances by stabilizing MTs and influencing cellular pathways that regulate reactive oxygen species (ROS). This modification is linked to enhanced antioxidant responses, autophagy regulation, and mitochondrial dynamics, highlighting its role in maintaining cellular homeostasis under oxidative conditions. The dual function of tubulin acetylation, responding to and integrating signals from mechanical and oxidative stress, acts as a bridging mechanism between physical and chemical signaling pathways. Consequently, it has the potential to be a therapeutic target in diseases characterized by dysregulated stress responses, including neurodegenerative disorders, cancer, and cardiovascular conditions. Despite significant progress having been made, unanswered questions persist, particularly regarding the molecular mechanisms by which acetylated MTs encode spatial and functional information and their interplay with other tubulin PTMs.engMechanical stressMicrotubuleOxidative stressTubulin acetylationTubulin post-translational modificationsIPL/IDI&CA2024/HyperCil_ESTeSLIPL/IDI&CA2024/ENIGMA_ESTeSLbook part10.1007/978-3-031-91459-1_5