Acetyl-Coenzyme A acyltransferase 2 attenuates the apoptotic effects of BNIP3 in two human cell lines

Biochim Biophys Acta. 2008 Jun;1780(6):873-80. doi: 10.1016/j.bbagen.2008.02.007. Epub 2008 Mar 6.


BNIP3 is a unique pro-apoptotic protein which belongs to the BH3-only subset of the Bcl-2 family and localizes on mitochondrial membrane. Despite the inherent difficulty of identifying binding partners for membrane proteins, several binding partners for BNIP3 have been identified. In this study, a modified split-ubiquitin membrane yeast two-hybrid system was constructed and used to identify acetyl-Coenzyme A acyltransferase 2 (ACAA2) as a new BNIP3 binding partner. The interaction between BNIP3 and ACAA2 was confirmed by pull-down and co-immunoprecipitation assays. ACAA2 was also found to co-localize with BNIP3 in mitochondria. Furthermore, the apoptosis induced by over-expressed BNIP3 via transfection or hypoxia treatment was abolished by ACAA2 in human hepatocellular carcinoma HepG2 cells and osteosarcoma U-2 OS cells. These results strongly suggest that ACAA2 be a functional BNIP3 binding partner and provide a possible linkage between fatty acid metabolism and apoptosis of cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl-CoA C-Acyltransferase / genetics
  • Acetyl-CoA C-Acyltransferase / metabolism*
  • Apoptosis / physiology*
  • Cell Line, Tumor
  • Fatty Acids / metabolism*
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mitochondrial Membranes / metabolism*
  • Protein Binding / physiology
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Two-Hybrid System Techniques


  • BNIP3 protein, human
  • Fatty Acids
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Acetyl-CoA C-Acyltransferase