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Cancer cells can use acid gradient across the plasma membrane to produce ATP
Author(s) -
Dhar Gautam,
Sen Suvajit,
Chaudhuri Gautam
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.915.7
Subject(s) - chemiosmosis , atp synthase , glycolysis , cancer cell , electrochemical gradient , biochemistry , mitochondrion , v atpase , mitochondrial matrix , chemistry , adenosine triphosphate , atpase , biophysics , atp hydrolysis , lactic acid , microbiology and biotechnology , metabolism , biology , membrane , cancer , enzyme , cytosol , bacteria , genetics
Cancer cells have enhanced glycolysis and less mitochondria mediated ATP synthesis. This leads to excess lactic acid production and acidification of the external matrix. Glycolysis generates 15–20 folds less ATP as compared to the mitochondria. Whether glycolysis can be a sufficient source of ATP for proliferating cancer cell, and why such switch occurs has always been debated. Acid gradient across membrane is an energy that can be utilized by ATP synthase to generate ATP. Published proteomics and microscopic data indicated the presence of ATP synthase subunits in the plasma membrane of cancer cells. Here we present evidence that cancer cells can utilize the acid gradient to produce large amount of ATP. ATP production starts at around pH 7.1‐6.8 depending on the cancer cell type, increases exponentially with lowering pH till pH 6.1‐6.3. This range resembles the reported pH for cancer cell environment. ATP production followed a dependence on the external proton concentration whose order depends on cancer cell type. ATP synthesis is very rapid at about 10 7 ‐10 8 ATP molecules/cell/s and depletes 3–5 protons from the external medium per ATP molecule, a value that closely resembles the ones published for other ATP synthases. Our work demonstrate that acidification of the external matrix through enhanced glycolysis is a strategy that enable cancer cells to harness the acid gradient for more efficient ATP production.