Mechanical Force Induces Mitochondrial Fission via the Canonical Fission Machinery

Qian Feng¹, Sebastian Helle¹, Benoît Kornmann^1*
¹Institute of Biochemistry, ETH Zurich, Zürich, Switzerland

Eukaryotic cells are densely packed with macromolecular complexes and intertwining membranous organelles that continually change shape and engage in active trafficking. It is intriguing that organelles avoid clashing and entangling with each other during such dynamic movements in such limited space. Here we describe a mechanism that explains how mitochondria orderly cohabit with other organelles in the crowded space of the cytoplasm. Mitochondria form extensive networks that are constantly remodeled by fission and fusion events. While the molecular machineries that execute mitochondrial fission and fusion processes are relatively well documented, little is known about what triggers these events and determines the fusion and fission sites. We show here that mechanical stimulation of mitochondria - via the encounter with motile intracellular pathogens, via external pressure applied by an atomic force microscope, or via cell migration across uneven microsurfaces - resulted in the recruitment of the canonical mitochondrial fission machinery and subsequent fission. The mitochondrial fission factor (MFF) acts as a membrane-bound force sensor preferentially accumulating at mitochondria of reduced diameter, then recruiting the fission machinery to sites of mechanical strain. Thus, mitochondria may avoid entanglement with itself and other cellular structures by responding to biomechanical cues. These results shed new light on mitochondrial dynamics, an important process that has been shown to influence cell migration, cardiovascular functions, neuronal plasticity, aging and more. That mechanical triggers can be coupled to biochemical responses in membrane dynamics also provides a new perspective in studying organelle communication in general.

Helle, S. C. J., Feng, Q., Aebersold, M. J., Hirt, L., Grüter, R. R., Vahid, A., … Kornmann, B. (2017). Mechanical force induces mitochondrial fission. eLife, 6, e30292. https://doi.org/10.7554/eLife.30292

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