Related Experiment Video
Updated: Aug 8, 2026

Characterizing the Composition of Molecular Motors on Moving Axonal Cargo Using "Cargo Mapping" Analysis
Published on: October 30, 2014
A molecular switch for coordinating kinesin and dynein transport of mitochondrial cargo
Christina Gladkova1, Maria G Paez-Segala1, William P Grant2
1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Abstract:
The cellular distribution of mitochondria in response to stress and local energy needs is governed by the relative activities of the microtubule-based molecular motors kinesin and dynein. The mechanism for switching between these two opposite-polarity microtubule motors remains unknown. In this study, we coupled a cellular synthetic cargo transport assay with AlphaFold2-guided mutagenesis to identify a regulatory helix in the mitochondrial adaptor protein [trafficking kinesin-binding protein (TRAK)] that mediates switching between kinesin- and dynein-driven transport. Differences in the helix sequence explained why two near-identical TRAK isoforms transported mitochondria in predominantly opposite directions. Phosphorylation of the regulatory helix by stress-activated kinases caused the activation of dynein and dissociation of kinesin. Our results reveal a molecular mechanism for coordinating the directional transport of mitochondria in response to intracellular signals.
Related Concept Videos
The Movement of Organelles and Vesicles
Microtubule Associated Motor Proteins
Energy to Drive Translocation
Generally, polypeptides are unfolded by two distinct...
Translocation of Proteins into the Mitochondria
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Mitochondrial Protein Sorting
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
The ADP/ATP Carrier Protein

