We show that this decrease in glycolytic capacity results in dramatically lowered free ATP levels in HIF-1α-deficient hypoxic cells
2002
Key concepts
Scholarcy highlights
- The ability to respond to differential levels of oxygen is important to all respiring cells
- Cells lacking HIF-1␣ exhibit decreased growth rates during hypoxia, as well as decreased levels of lactic acid production and decreased acidosis. We show that this decrease in glycolytic capacity results in dramatically lowered free ATP levels in HIF-1␣-deficient hypoxic cells
- Recent data from our laboratory demonstrated that tumors derived from transformed HIF-1␣-null fibroblasts created via cre-loxP recombinase-mediated deletion of HIF-1␣ were smaller than those derived from wild-type cells
- The relative vascular density was similar in these two tumor types. Because this finding implied that some other mechanism of transformed cell growth was deficient in cells lacking HIF-1␣, we began to evaluate other likely deficiencies in the ability of HIF-1␣-null cells to withstand hypoxia
- We demonstrate a critical requirement for the transcription factor HIF-1 in controlling this shift to glycolysis
- We argue that HIF-1 is a critical integrator of cellular adaptation to hypoxia because, in the absence of HIF-1␣, otherwise genetically identical cells show physiologically significant alterations in energy metabolism
- We began to characterize the changes in global protein expression during hypoxia in wild-type and null cells to determine the overall profile of changes controlled at the proteomic level by HIF-1␣
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