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Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1
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Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1

Published on: February 25, 2016

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Evidence for mitochondrial localization of divalent metal transporter 1 (DMT1)

Natascha A Wolff1, Andrew J Ghio, Laura M Garrick

  • 11Department of Physiology and Pathophysiology and ZBAF, University of Witten/Herdecke, Stockumer Strasse 12, D-58453 Witten, Germany. F.T., frank.thevenod@uni-wh.de.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|January 23, 2014
PubMed

Insights

Divalent metal transporter 1 (DMT1) is found in the outer mitochondrial membrane, acting as a novel iron import pathway into mitochondria. This discovery reveals a new mechanism for cellular iron regulation.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Mitochondria are crucial for cellular iron metabolism, receiving the majority of incoming iron.
  • The specific pathway for iron entry into the outer mitochondrial membrane (OMM) has remained uncharacterized.

Purpose of the Study:

  • To identify the protein responsible for iron transport across the OMM.
  • To elucidate the mechanism of mitochondrial iron uptake.

Main Methods:

  • Immunoblotting and immunofluorescence assays to detect DMT1 localization.
  • Split-ubiquitin yeast two-hybrid system to identify interacting proteins.
  • Co-immunoprecipitation assays.
  • Cell fractionation and immunogold labeling.

Main Results:

  • Divalent metal transporter 1 (DMT1) was detected in the OMM of mammalian cells, including pneumocytes and kidney cells.
  • DMT1 was found to interact with cytochrome c oxidase subunit II (COXII) and Tom6.
  • All four known isoforms of DMT1 were localized to the OMM.
  • DMT1 colocalized with the voltage-dependent anion-selective channel protein-1 in mitochondria.

Conclusions:

  • DMT1 functions as an iron importer into the OMM.
  • This identifies DMT1 as a key player in mitochondrial iron uptake, in addition to its role in endosomal iron export.
Keywords:
adenine nucleotide translocatorearly endosomal antigen 1kiss-and-runlysosome-associated membrane proteintransferrin

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