TRIAP1/PRELI complexes prevent apoptosis by mediating intramitochondrial transport of phosphatidic acid

Cell Metab. 2013 Aug 6;18(2):287-95. doi: 10.1016/j.cmet.2013.07.008.


Cardiolipin (CL), a mitochondria-specific glycerophospholipid, is required for diverse mitochondrial processes and orchestrates the function of various death-inducing proteins during apoptosis. Here, we identify a complex of the p53-regulated protein TRIAP1 (p53CSV) and PRELI in the mitochondrial intermembrane space (IMS), which ensures the accumulation of CL in mitochondria. TRIAP1/PRELI complexes exert lipid transfer activity in vitro and supply phosphatidic acid (PA) for CL synthesis in the inner membrane. Loss of TRIAP1 or PRELI impairs the accumulation of CL, facilitates the release of cytochrome c, and renders cells vulnerable to apoptosis upon intrinsic and extrinsic stimulation. Survival of TRIAP1- and PRELI-deficient cells is conferred by an excess of exogenously provided phosphatidylglycerol. Our results reveal a p53-dependent cell-survival pathway and highlight the importance of the CL content of mitochondrial membranes in apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Apoptosis*
  • Biological Transport
  • Cardiolipins / metabolism
  • Cell Line
  • Cell Survival
  • Cytochromes c / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / deficiency
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mitochondria / metabolism*
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Proteins / deficiency
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Multiprotein Complexes / metabolism
  • Phosphatidic Acids / metabolism*
  • Phosphatidylglycerols / metabolism
  • RNA Interference
  • RNA, Small Interfering
  • Sequence Alignment
  • Signal Transduction


  • Cardiolipins
  • Intracellular Signaling Peptides and Proteins
  • Mitochondrial Proteins
  • Multiprotein Complexes
  • PRELID1 protein, human
  • Phosphatidic Acids
  • Phosphatidylglycerols
  • RNA, Small Interfering
  • TRIAP1 protein, human
  • Cytochromes c