University of Pittsburgh Cancer Institute (UPCI)

Mitochondria and Metabolism

Mitochondria in a Dividing Cell The mitochondrial apoptotic pathway is activated by many types of cellular stress, and when initiated, causes programmed death. One hallmark of cancer cells is their ability to overcome apoptotic signals of cell death. Metabolic changes are another hallmark of cancer, and the nature of cellular bioenergetics in tumor cells is an area of active research. MCCBP investigators are involved in studies of cellular metabolism, apoptosis, and mitochondrial physiology in normal and cancer cells.

Selected Publications

  • Withaferin A (WA), a promising anticancer constituent of Ayurvedic medicinal plant Withania somnifera, inhibits growth of human breast cancer cells in culture and in vivo in association with apoptosis induction, which is mediated by activation of the pro-apoptotic proteins Bax and Bak (Hahm ER, et. al., PLoS One 6:e23354, 2011).
  • Autophagy is an evolutionarily conserved stress response mechanism that often occurs in apoptosis-defective cancer cells and can protect against cell death. Results show that chemotherapy-induced apoptosis inhibits autophagy at the execution stage subsequent to cytochrome c release through caspase 8-mediated cleavage of Beclin 1. If apoptosis fails to execute, autophagy is unleashed due to lack of Beclin 1 cleavage by caspases and can contribute to cancer cell survival and therapeutic resistance (Li H, et. al., Cancer Res 71:3625-34, 2011).
  • Mitochondria are organelles centrally important for bioenergetics as well as regulation of apoptotic death in eukaryotic cells. High-mobility group box 1 (HMGB1), an evolutionarily conserved chromatin-associated protein which maintains nuclear homeostasis, is also a critical regulator of mitochondrial function and morphology. An essential role for HMGB1 and its downstream effector HspB1 was found in autophagic surveillance with important effects on mitochondrial physiology quality control (Tang D, et. al., Cell Metab 13:701-11, 2011).

Members

Lee, Yong, PhD
Surgery
Van Houten, Ben, PhD
Pharmacology and Chemical Biology
Prochownik, Edward, MD, PhD
Pediatrics
Yu, Jian, PhD
Pathology
Sobol, Robert, PhD
Pharmacology and Chemical Biology
Zhang, Lin, PhD
Pharmacology and Chemical Biology