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Cited by 131Microtubule and mitosis dynamicsMitochondrial Function and PathologyAutophagy in Disease and Therapy

TRAK adaptors regulate the recruitment and activation of dynein and kinesin in mitochondrial transport

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Canty, John T., Hensley, Andrew, Aslan, Merve, Jack, Amanda, Yildiz, Ahmet·2023·Nature Communications
DOI 10.1038/s41467-023-36945-8PMC PMC10011603

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Abstract

Mitochondrial transport along microtubules is mediated by Miro1 and TRAK adaptors that recruit kinesin-1 and dynein-dynactin. To understand how these opposing motors are regulated during mitochondrial transport, we reconstitute the bidirectional transport of Miro1/TRAK along microtubules in vitro. We show that the coiled-coil domain of TRAK activates dynein-dynactin and enhances the motility of kinesin-1 activated by its cofactor MAP7. We find that TRAK adaptors that recruit both motors move towards kinesin-1’s direction, whereas kinesin-1 is excluded from binding TRAK transported by dynein-dynactin, avoiding motor tug-of-war. We also test the predictions of the models that explain how mitochondrial transport stalls in regions with elevated Ca 2+ . Transport of Miro1/TRAK by kinesin-1 is not affected by Ca 2+ . Instead, we demonstrate that the microtubule docking protein syntaphilin induces resistive forces that stall kinesin-1 and dynein-driven motility. Our results suggest that mitochondrial transport stalls by Ca 2+ -mediated recruitment of syntaphilin to the mitochondrial membrane, not by disruption of the transport machinery.

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Cited by

Sorted by citations

Authors
Canty, J. T., Hensley, A., Aslan, M., Jack, A., & Yildiz, A.
Affiliations
  • Genentech (US)
  • University of California, Berkeley (US)
Corresponding author
Canty, John T.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2023-03-13
Volume
14
Issue
1
Pages
1376-1376
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-023-36945-8
PMC
PMC10011603
OpenAlex
W4324129195
Cited by
131
References
3
Citations by year
2026: 37 · 2025: 34 · 2024: 30 · 2023: 19 · 2022: 9 · 2021: 2
FWCI
17.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • NSF | Directorate for Education & Human Resources | Division of Graduate Education (DGE-1752814)
  • U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (GM136414)
  • NSF | BIO | Division of Molecular and Cellular Biosciences (MCB-1055017, MCB-1617028)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
mitochondrial transport, Miro1, kinesin-1, dynein/dynactin, bidirectional transport, microtubules, coiled-coil domain, MAP7, syntaphilin, calcium, resistance force
MeSH terms
Dynactin Complex, Biological Transport, Dyneins, Microtubule-Associated Proteins, Microtubules, Kinesins

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