Related Experiment Video
Updated: Mar 16, 2026

Author Spotlight: Transmitochondrial Cybrid Generation Using Cancer Cell Lines
Published on: March 17, 2023
Mitochondrial Akt Regulation of Hypoxic Tumor Reprogramming
Young Chan Chae1, Valentina Vaira2, M Cecilia Caino1
1Prostate Cancer Discovery and Development Program, Tumor Microenvironment and Metastasis Program, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Abstract:
Hypoxia is a universal driver of aggressive tumor behavior, but the underlying mechanisms are not completely understood. Using a phosphoproteomics screen, we now show that active Akt accumulates in the mitochondria during hypoxia and phosphorylates pyruvate dehydrogenase kinase 1 (PDK1) on Thr346 to inactivate the pyruvate dehydrogenase complex. In turn, this pathway switches tumor metabolism toward glycolysis, antagonizes apoptosis and autophagy, dampens oxidative stress, and maintains tumor cell proliferation in the face of severe hypoxia. Mitochondrial Akt-PDK1 signaling correlates with unfavorable prognostic markers and shorter survival in glioma patients and may provide an "actionable" therapeutic target in cancer.
Related Concept Videos
Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
mTOR Signaling and Cancer Progression
PI3K/mTOR/AKT Signaling Pathway
Regulation of Angiogenesis and Blood Supply

