Metabolic depletion inhibits the uptake of nontransferrin-bound iron by K562 cells.
The effect of metabolic inhibitors on nontransferrin bound iron transport by K562 cells was investigated. Incubation with 1 microM rotenone, 10 microM antimycin, or 0.5 mM 2,4-dinitrophenol effectively reduced ATP levels by approximately 50%. Both the rate and extent of Fe+3 uptake were impaired in ATP-depleted cells, which display a reduced Vmax for uptake. K562 cell ferrireductase activity was also lowered by metabolic inhibitors, suggesting that the apparent energy requirements for transport reside in the reduction of Fe+3 to Fe+2. However, ATP depletion was found to inhibit the rate and extent of Fe+2 uptake as well. Thus, the transbilayer passage of Fe+2 and/or Fe+3 appears to be an energy-requiring process. These features possibly reflect properties of the transport mechanism associated with a recently identified K562 cell transport protein, called SFT for "Stimulator of Fe Transport," since exogenous expression of its activity is also affected by ATP depletion.
Gutierrez
J A
JA
Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Inman
R S
RS
Akompong
T
T
Yu
J
J
Wessling-Resnick
M
M
D019297:2,4-Dinitrophenol / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000172:deficiency / Q000502:physiology; D000968:Antimycin A / Q000031:analogs & derivatives / Q000494:pharmacology; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D038181:FMN Reductase; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins; D020014:K562 Cells / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology; D044763:Ubiquitin-Conjugating Enzymes; D014475:Uncoupling Agents / Q000494:pharmacology*
D002352:Carrier Proteins; D033862:Iron-Binding Proteins; D014475:Uncoupling Agents; D012402:Rotenone; C032456:antimycin; D000968:Antimycin A; D000255:Adenosine Triphosphate; D007501:Iron; D038181:FMN Reductase; D009247:NADH, NADPH Oxidoreductases; C023903:ferric citrate iron reductase; C097308:UBE2D1 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D019297:2,4-Dinitrophenol