Mechanical forces on cellular organelles

The intracellular environment of eukaryotic cells is highly complex and compact. The limited volume of the cell, usually a few hundred femtoliters, is not only occupied by numerous complicated, diverse membranous and proteinaceous structures, these structures are also highly dynamic due to constant remodeling and trafficking events. Consequently, intracellular interactions are more than just opportunities to exchange molecules; they also involve components physically navigating around each other in a highly confined space. While the biochemical interactions between organelles have been intensely studied in the past decades, the mechanical properties of organelles and the physical interactions between them are only beginning to be unraveled. Indeed, recent studies show that intracellular organelles are, at times, under extreme mechanical strain both in widely used experimental systems as well as in vivo. In this Hypothesis, we highlight known examples of intracellular mechanical challenges in biological systems and focus on the coping mechanisms of two important organelles, the nucleus and mitochondria, for they are the best studied in this aspect. In the case of mitochondria, we propose that ER–mitochondrial contact sites at thin cell peripheries may induce mitochondrial fission by mechanically constricting mitochondrial tubules. We also briefly discuss the mechano-responsiveness of other organelles and interesting directions for future research.