Mechanical force induces mitochondrial fission
Sebastian Carsten Johannes Helle (ETH Zürich)
Qian Feng (ETH Zürich)
Mathias J. Aebersold (ETH Zürich)
Luca Hirt (ETH Zürich)
Raphael R. Grüter (ETH Zürich)
A. Vahid Belarghou (Kavli institute of nanoscience Delft, TU Delft - BN/Timon Idema Lab)
Andrea Sirianni (Imperial College London)
Serge Mostowy (Imperial College London)
Jess G. Snedeker (ETH Zürich, Universitat Zurich)
Anđela Šarić (University College London)
Timon Idema (Kavli institute of nanoscience Delft, TU Delft - BN/Timon Idema Lab)
Tomaso Zambelli (ETH Zürich)
Benoît Kornmann (ETH Zürich)
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Abstract
Eukaryotic cells are densely packed with macromolecular complexes and intertwining organelles, continually transported and reshaped. Intriguingly, organelles avoid clashing and entangling with each other in such limited space. Mitochondria form extensive networks constantly remodeled by fission and fusion. Here, we show that mitochondrial fission is triggered by mechanical forces. Mechano-stimulation of mitochondria - via encounter with motile intracellular pathogens, via external pressure applied by an atomic force microscope, or via cell migration across uneven microsurfaces - results in the recruitment of the mitochondrial fission machinery, and subsequent division. We propose that MFF, owing to affinity for narrow mitochondria, acts as a membrane-bound force sensor to recruit the fission machinery to mechanically strained sites. Thus, mitochondria adapt to the environment by sensing and responding to biomechanical cues. Our findings that mechanical triggers can be coupled to biochemical responses in membrane dynamics may explain how organelles orderly cohabit in the crowded cytoplasm.
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