Human Miltons associate with mitochondria and induce microtubule-dependent remodeling of mitochondrial networks

Koutsopoulos, Olga S., Laine, David, Osellame, Laura, Chudakov, Dmitriy M., Parton, Robert G., Frazier, Ann E. and Ryan, Michael T. (2010) Human Miltons associate with mitochondria and induce microtubule-dependent remodeling of mitochondrial networks. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1803 5: 564-574. doi:10.1016/j.bbamcr.2010.03.006


Author Koutsopoulos, Olga S.
Laine, David
Osellame, Laura
Chudakov, Dmitriy M.
Parton, Robert G.
Frazier, Ann E.
Ryan, Michael T.
Title Human Miltons associate with mitochondria and induce microtubule-dependent remodeling of mitochondrial networks
Journal name Biochimica et Biophysica Acta (BBA) - Molecular Cell Research   Check publisher's open access policy
ISSN 0167-4889
Publication date 2010-05
Sub-type Article (original research)
DOI 10.1016/j.bbamcr.2010.03.006
Volume 1803
Issue 5
Start page 564
End page 574
Total pages 11
Place of publication Amsterdam
Publisher Elsevier BV
Collection year 2011
Language eng
Formatted abstract
Proper mitochondrial distribution is crucial for cell function. In Drosophila, mitochondrial transport is facilitated by Miro and Milton, which regulate mitochondrial attachment to microtubules via kinesin heavy chain. Mammals contain two sequence orthologs of Milton however, they have been ascribed various functions in intracellular transport. In this report, we show that the human Miltons target to mitochondria irrespective of whether they are linked to GFP at their C- or N-termini. Their ectopic expression induces the formation of extended mitochondrial tubules as well as large bulbous-like mitochondria with narrow tubular membrane necks that connect them to the mitochondrial mass. The mitochondrial extensions appear highly dynamic and their formation relies on the presence of microtubules. Using the photoswitchable fluorescent protein Dendra2 targeted to the mitochondrial matrix, we found that the mitochondrial extensions and bulbous mitochondria are fused with neighboring regions of the network. Truncation analysis of huMilton1 revealed that the N-terminal region, inclusive of the coiled-coil segment could localize to microtubules, suggesting that Milton attachment to kinesin occurs independent of Miro or mitochondrial attachment. In addition, we show that the huMiltons have the capacity to self-interact and can also facilitate mitochondrial recruitment of a cytosolic Miro mutant. We conclude that the human Miltons are important mediators of the mitochondrial trafficking machinery.
Copyright © 2010 Elsevier B.V. All rights reserved.

Keyword Mitochondria
Morphology
Distribution
Trafficking
Milton
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Institute for Molecular Bioscience - Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 30 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 06 Jun 2010, 00:07:46 EST