Mechanical forces on cellular organelles

Abstract

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.

Human muscular mitochondrial fusion in athletes during exercise

“…To our knowledge, there are no previous findings reporting mitochondrial morphologic changes in different orientations in response to exercise. Nevertheless, it has been recently reported that mechanical forces can promote mitochondrial morphology changes leading to fragmentation (2, 50). The fact that we observed a down‐regulation of FIS1 and MFF gene expression led to the hypothesis that mitochondrial morphologic changes in response to HIHVT may occur in response to intramuscular forces by which mitochondria are getting squashed between muscle fibers.…”

Mitochondrial membrane tension governs fission

“…could change the local mechanical properties at the constriction site[55], facilitating division. Finally, mitochondrial division has been observed to take place near replicating nucleoids[56] the presence of which might create 'rigid islands' that increase bending energies at adjacent constriction sites[57], making them more likely to divide according to our model. Such internal mechanisms could simultaneously control the positioning and fate of mitochondrial constrictions.…”

Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction

“…This metabolic reprogramming is quite evident during stem cell transition from self-renewal to differentiation [151] and can be the result of the specific activated gene program. However, since the shift in the metabolism often precedes cell fate establishment, it may play a permissive or instructive role on cell commitment [152][153][154].…”

“…All the three cytoskeletal components-actin, intermediate filaments, and microtubules-interact with mitochondria; they can act as rails to support mitochondrial movement, or they can control mitochondria shape, network organization, and confinement in subdomains with high metabolic demands [156][157][158]. Therefore, it is not surprising that biophysical forces, by modifying the cytoskeletal organization, can also remodel mitochondria [153].…”