Shifting the paradigm: the putative mitochondrial protein ABCB6 resides in the lysosomes of cells and in the plasma membrane of erythrocytes.
ABCB6, a member of the adenosine triphosphate-binding cassette (ABC) transporter family, has been proposed to be responsible for the mitochondrial uptake of porphyrins. Here we show that ABCB6 is a glycoprotein present in the membrane of mature erythrocytes and in exosomes released from reticulocytes during the final steps of erythroid maturation. Consistent with its presence in exosomes, endogenous ABCB6 is localized to the endo/lysosomal compartment, and is absent from the mitochondria of cells. Knock-down studies demonstrate that ABCB6 function is not required for de novo heme biosynthesis in differentiating K562 cells, excluding this ABC transporter as a key regulator of porphyrin synthesis. We confirm the mitochondrial localization of ABCB7, ABCB8 and ABCB10, suggesting that only three ABC transporters should be classified as mitochondrial proteins. Taken together, our results challenge the current paradigm linking the expression and function of ABCB6 to mitochondria.
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
Katalin
K
Kiss
Anna
A
Brozik
Nora
N
Kucsma
Alexandra
A
Toth
Melinda
M
Gera
Laurence
L
Berry
Alice
A
Vallentin
Henri
H
Vial
Michel
M
Vidal
Gergely
G
Szakacs
D018528:ATP-Binding Cassette Transporters / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D008247:Lysosomes / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism
C107991:ABCB6 protein, human; D018528:ATP-Binding Cassette Transporters; D006454:Hemoglobins; D024101:Mitochondrial Proteins