APC binds the miro/Milton motor complex to stimulate transport of mitochondria to the plasma membrane

Kate M. Mills, Mariana G. Brocardo, Beric R. Henderson

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Mutations in adenomatous polyposis coli (APC) disrupt regulation of Wnt signaling, mitosis, and the cytoskeleton. We describe a new role for APC in the transport of mitochondria. Silencing of wild-type APC by small interfering RNA caused mitochondria to redistribute from the cell periphery to the perinuclear region. We identified novel APC interactions with the mitochondrial kinesin-motor complex Miro/Milton that were mediated by the APC C-terminus. Truncating mutations in APC abolished its ability to bind Miro/Milton and reduced formation of the Miro/Milton complex, correlating with disrupted mitochondrial distribution in colorectal cancer cells that could be recovered by reconstitution of wild-type APC. Using proximity ligation assays, we identified endogenous APC-Miro/Milton complexes at mitochondria, and live-cell imaging showed that loss of APC slowed the frequency of anterograde mitochondrial transport to the membrane. We propose that APC helps drive mitochondria to the membrane to supply energy for cellular processes such as directed cell migration, a process disrupted by cancer mutations.

LanguageEnglish
Pages466-482
Number of pages17
JournalMolecular Biology of the Cell
Volume27
Issue number3
DOIs
Publication statusPublished - 1 Feb 2016
Externally publishedYes

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Adenomatous Polyposis Coli
Mitochondria
Cell Membrane
Mutation
Kinesin
Membranes
Cytoskeleton
Mitosis
Small Interfering RNA
Cell Movement
Ligation
Colorectal Neoplasms

Bibliographical note

Copyright the Author(s) 2016. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Cite this

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APC binds the miro/Milton motor complex to stimulate transport of mitochondria to the plasma membrane. / Mills, Kate M.; Brocardo, Mariana G.; Henderson, Beric R.

In: Molecular Biology of the Cell, Vol. 27, No. 3, 01.02.2016, p. 466-482.

Research output: Contribution to journalArticleResearchpeer-review

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