title: Mitochondria represent another locale for the divalent metal transporter 1 (DMT1).
abstract: The divalent metal transporter (DMT1) is well known for its roles in duodenal iron absorption across the apical enterocyte membrane, in iron efflux from the endosome during transferrin-dependent cellular iron acquisition, as well as in uptake of non-transferrin bound iron in many cells. Recently, using multiple approaches, we have obtained evidence that the mitochondrial outer membrane is another subcellular locale of DMT1 expression. While iron is of vital importance for mitochondrial energy metabolism, its delivery is likely to be tightly controlled due to iron's damaging redox properties. Here we provide additional support for a role of DMT1 in mitochondrial iron acquisition by immunofluorescence colocalization with mitochondrial markers in cells and isolated mitochondria, as well as flow cytometric quantification of DMT1-positive mitochondria from an inducible expression system. Physiological consequences of mitochondrial DMT1 expression are discussed also in consideration of other DMT1 substrates, such as manganese, relevant to mitochondrial antioxidant defense.
authors.affiliation: a Institute of Physiology; Pathophysiology & Toxicology ; University of Witten/Herdecke ; Witten , Germany.
authors.forename: Natascha A
authors.initials: NA
authors.lastname: Wolff
authors.forename: Laura M
authors.initials: LM
authors.lastname: Garrick
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.forename: Michael D
authors.initials: MD
authors.lastname: Garrick
authors.forename: Frank
authors.initials: F
authors.lastname: Thévenod
mesh_terms: D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C110547:DMRT1 protein; D014157:Transcription Factors
keywords: AIF, apoptosis-inducing factor; BSA, bovine serum albumin; CHO, Chinese hamster ovary; COXII, cytochrome C oxidase subunit II; DMT1, divalent metal transporter 1; HEK293, human embryonic kidney cells; IRE, iron responsive element; Lamp1, lysosome-associated membrane protein 1; MRB, Mitochondrial Resuspending Buffer; OMM, outer mitochondrial membrane; PBS, phosphate-buffered saline; Tf, transferrin; Tom6/Tom20, translocase of the outer mitochondrial membrane 6 kDa subunit homolog/20 kDa subunit, respectively; VDAC1, voltage-dependent anion-selective channel protein 1; divalent metal transporter 1 (DMT1); flow cytometry; immunofluorescence microscopy; iron transport; mitochondrial outer membrane