期刊
AMINO ACIDS
卷 35, 期 4, 页码 681-690出版社
SPRINGER WIEN
DOI: 10.1007/s00726-008-0063-4
关键词
proline oxidase; proline dehydrogenase; mTOR; PPAR gamma; apoptosis; bioenergetics
资金
- Intramural NIH HHS Funding Source: Medline
- NCI NIH HHS [N01-CO-12400] Funding Source: Medline
The resurgence of interest in tumor metabolism has led investigators to emphasize the metabolism of proline as a stress substrate and to suggest this pathway as a potential anti-tumor target. Proline oxidase, a.k.a. proline dehydrogenase (POX/PRODH), catalyzes the first step in proline degradation and uses proline to generate ATP for survival or reactive oxygen species for programmed cell death. POX/PRODH is induced by p53 under genotoxic stress and initiates apoptosis by both mitochondrial and death receptor pathways. Furthermore, POX/PRODH is induced by PPAR gamma and its pharmacologic ligands, the thiazolidinediones. The anti-tumor effects of PPAR gamma may be critically dependent on POX/PRODH. In addition, it is upregulated by nutrient stress through the mTOR pathway to maintain ATP levels. We propose that proline is made available as a stress substrate by the degradation of collagen in the microenvironmental extracellular matrix by matrix metalloproteinases. In a manner analogous to autophagy, this proline-dependent process for bioenergetics from collagen in extracellular matrix can be designated ecophagy.
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