Mitochondria move smoothly through crowded environment

An international team led by researchers from the Institute of Biotechnology of the Czech Academy of Sciences describes a mechanism underlying transport of organelles within cells. The work shows how long-range transport can efficiently work in crowded cellular environments.

Mitochondria, organelles that produce cellular energy, need to be transported within cells to places of high energy demand. Mitochondrial transport is driven by motor proteins, which move the mitochondria along intracellular paths formed by filaments called microtubules. Severe pathologies, such as neurodegeneration, arise when mitochondrial transport is faulty, yet the mechanisms underlying mitochondrial motion are not fully understood. In particular, it is not clear how mitochondria can proceed along the microtubules while their route is occupied by densely packed proteins that block the microtubules.

An international team of scientists from the Institute of Biotechnology of the Czech Academy of Sciences, located in the BIOCEV Research Centre in Prague and the Technical University in Dresden found that the adaptor protein TRAK1, by tethering the mitochondria to the microtubules, provides additional adhesion that stabilizes the mitochondria-microtubule interaction. While this extra adhesion reduces speed, it makes the transport much more reliable over longer distances and provides the motor protein that drives the transport with extra time to find viable path that allows passing through the protein crowds.

Verena Henrichs, the first author of the study explains the underlying mechanism: “We found that the mitochondrial adaptor protein TRAK1 tethers the motor protein kinesin to cytoskeletal filaments. This tethering decreases the likelihood of kinesin to detach from the microtubule and thus allows the kinesin-TRAK1 complex to walk over long distances. One can imagine the tethering analogous to rope climbing: if a climber (the motor protein kinesin) loses hold of the wall (the microtubule), the climber will fall off and cannot continue its climb. By contrast, if belayed by a rope (TRAK1), the climber can regain his grip, even after temporarily losing hold, and thus can continue his ascent.”

The study shows that TRAK1-tethering promotes kinesin-driven transport in crowded environments in which all available footholds are often occupied, and thus facilitates mitochondrial transport over long distances.

Original paper: Henrichs, V., Grycova, L., Barinka, C., Nahacka, Z., Neuzil, J., Diez, S., Rohlena, J., Braun, M. and Lansky, Z. (2020). Mitochondria-adaptor TRAK1 promotes kinesin-1 driven transport in crowded environments. Nature Communications 11, 3123. https://doi.org/10.1038/s41467-020-16972-5