ER-mitochondria contacts promote mtDNA nucleoids active transportation via mitochondrial dynamic tubulation.

Qin, J; Guo, Y; Xue, B; Shi, P; Chen, Y; Su, QP; Hao, H; Zhao, S; Wu, C; Yu, L; Li, D; Sun, Y

ER-mitochondria contacts promote mtDNA nucleoids active transportation via mitochondrial dynamic tubulation.

Qin, J Guo, Y Xue, B Shi, P Chen, Y Su, QP Hao, H Zhao, S Wu, C Yu, L Li, D Sun, Y

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Publisher:: Springer Science and Business Media LLC
Publication Type:: Journal Article
Citation:: Nature communications, 2020, 11, (1), pp. 4471
Issue Date:: 2020-09-08

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Field	Value	Language
dc.contributor.author	Qin, J
dc.contributor.author	Guo, Y
dc.contributor.author	Xue, B
dc.contributor.author	Shi, P
dc.contributor.author	Chen, Y
dc.contributor.author	Su, QP
dc.contributor.author	Hao, H
dc.contributor.author	Zhao, S
dc.contributor.author	Wu, C
dc.contributor.author	Yu, L
dc.contributor.author	Li, D
dc.contributor.author	Sun, Y
dc.date.accessioned	2020-12-29T03:36:14Z
dc.date.available	2020-08-06
dc.date.available	2020-12-29T03:36:14Z
dc.date.issued	2020-09-08
dc.identifier.citation	Nature communications, 2020, 11, (1), pp. 4471
dc.identifier.issn	2041-1723
dc.identifier.issn	2041-1723
dc.identifier.uri	http://hdl.handle.net/10453/144990
dc.description.abstract	A human cell contains hundreds to thousands of mitochondrial DNA (mtDNA) packaged into nucleoids. Currently, the segregation and allocation of nucleoids are thought to be passively determined by mitochondrial fusion and division. Here we provide evidence, using live-cell super-resolution imaging, that nucleoids can be actively transported via KIF5B-driven mitochondrial dynamic tubulation (MDT) activities that predominantly occur at the ER-mitochondria contact sites (EMCS). We further demonstrate that a mitochondrial inner membrane protein complex MICOS links nucleoids to Miro1, a KIF5B receptor on mitochondria, at the EMCS. We show that such active transportation is a mechanism essential for the proper distribution of nucleoids in the peripheral zone of the cell. Together, our work identifies an active transportation mechanism of nucleoids, with EMCS serving as a key platform for the interplay of nucleoids, MICOS, Miro1, and KIF5B to coordinate nucleoids segregation and transportation.
dc.format	Electronic
dc.language	eng
dc.publisher	Springer Science and Business Media LLC
dc.relation	http://purl.org/au-research/grants/nhmrc/APP1177374
dc.relation	National Heart Foundation of Australia102592
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT1177374
dc.relation.ispartof	Nature communications
dc.relation.isbasedon	10.1038/s41467-020-18202-4
dc.rights	This is a post-peer-review, pre-copyedit version of an article published in Nature communications. The final authenticated version is available online at: https://dx.doi.org/10.1038/s41467-020-18202-4.	en_US
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.mesh	Cells, Cultured
dc.subject.mesh	COS Cells
dc.subject.mesh	Endoplasmic Reticulum
dc.subject.mesh	Mitochondria
dc.subject.mesh	Animals
dc.subject.mesh	Humans
dc.subject.mesh	Mice
dc.subject.mesh	Rats
dc.subject.mesh	Kinesin
dc.subject.mesh	rho GTP-Binding Proteins
dc.subject.mesh	Membrane Transport Proteins
dc.subject.mesh	DNA-Binding Proteins
dc.subject.mesh	Receptors, Cell Surface
dc.subject.mesh	Mitochondrial Proteins
dc.subject.mesh	Transcription Factors
dc.subject.mesh	DNA, Mitochondrial
dc.subject.mesh	Transfection
dc.subject.mesh	Biological Transport, Active
dc.subject.mesh	Models, Biological
dc.subject.mesh	Mitochondrial Membranes
dc.subject.mesh	HEK293 Cells
dc.subject.mesh	Mitochondrial Dynamics
dc.subject.mesh	Chlorocebus aethiops
dc.subject.mesh	Animals
dc.subject.mesh	Biological Transport, Active
dc.subject.mesh	COS Cells
dc.subject.mesh	Cells, Cultured
dc.subject.mesh	Chlorocebus aethiops
dc.subject.mesh	DNA, Mitochondrial
dc.subject.mesh	DNA-Binding Proteins
dc.subject.mesh	Endoplasmic Reticulum
dc.subject.mesh	HEK293 Cells
dc.subject.mesh	Humans
dc.subject.mesh	Kinesin
dc.subject.mesh	Membrane Transport Proteins
dc.subject.mesh	Mice
dc.subject.mesh	Mitochondria
dc.subject.mesh	Mitochondrial Dynamics
dc.subject.mesh	Mitochondrial Membranes
dc.subject.mesh	Mitochondrial Proteins
dc.subject.mesh	Models, Biological
dc.subject.mesh	Rats
dc.subject.mesh	Receptors, Cell Surface
dc.subject.mesh	Transcription Factors
dc.subject.mesh	Transfection
dc.subject.mesh	rho GTP-Binding Proteins
dc.title	ER-mitochondria contacts promote mtDNA nucleoids active transportation via mitochondrial dynamic tubulation.
dc.type	Journal Article
utslib.citation.volume	11
utslib.location.activity	England
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	open_access	*
dc.date.updated	2020-12-29T03:35:44Z
pubs.issue	1
pubs.publication-status	Published
pubs.volume	11
utslib.citation.issue	1

Abstract:

A human cell contains hundreds to thousands of mitochondrial DNA (mtDNA) packaged into nucleoids. Currently, the segregation and allocation of nucleoids are thought to be passively determined by mitochondrial fusion and division. Here we provide evidence, using live-cell super-resolution imaging, that nucleoids can be actively transported via KIF5B-driven mitochondrial dynamic tubulation (MDT) activities that predominantly occur at the ER-mitochondria contact sites (EMCS). We further demonstrate that a mitochondrial inner membrane protein complex MICOS links nucleoids to Miro1, a KIF5B receptor on mitochondria, at the EMCS. We show that such active transportation is a mechanism essential for the proper distribution of nucleoids in the peripheral zone of the cell. Together, our work identifies an active transportation mechanism of nucleoids, with EMCS serving as a key platform for the interplay of nucleoids, MICOS, Miro1, and KIF5B to coordinate nucleoids segregation and transportation.

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http://hdl.handle.net/10453/144990