Overexpression of proline oxidase induces proline-dependent and mitochondria-mediated apoptosis

Chien An Hu, Steven P. Donald, Jian Yu, Wei Wen Lin, Zhihe Liu, Gary Steel, Cassandra Obie, David Valle, James M. Phang

Research output: Contribution to journalArticle

Abstract

Proline oxidase (POX), a mitochondrial inner-membrane protein, catalyzes the rate-limiting oxidation of proline to pyrroline-5-carboxylate (P5C). Previously we showed that overexpression of POX is associated with generation of reactive oxygen species (ROS) and apoptosis in POX-inducible colorectal cancer cells, DLD-1.POX. We also showed expression of mitochondrial MnSOD partially blunts POX-induced ROS generation and apoptosis. To further investigate the molecular basis of POX-induced apoptosis, we utilized the DLD-1.POX cells to show that cells overproducing POX exhibit an L-proline-dependent apoptotic response. The apoptotic effect is specific for L-proline, detectable at 0.2 mM, maximal at 1 mM, and occurs during 48-72 h following the addition of L-proline to cells with maximally induced POX. The apoptotic response is mitochondria-mediated with release of cytochrome c, activation of caspase-9, chromatin condensation/DNA fragmentation, and cell shrinkage. We conclude that in the presence of proline, high POX activity is sufficient to induce mitochondria-mediated apoptosis.

Original languageEnglish (US)
Pages (from-to)85-92
Number of pages8
JournalMolecular and Cellular Biochemistry
Volume295
Issue number1-2
DOIs
StatePublished - Jan 1 2007

Keywords

  • Apoptosis
  • Mitochondria
  • Proline oxidase
  • Proline-P5C cycle
  • Reactive oxygen species
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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