ApoL1, a BH3-only lipid-binding protein, induces autophagic cell death

Autophagy. 2008 Nov;4(8):1079-82. doi: 10.4161/auto.7066. Epub 2008 Nov 23.


We recently reported the identification and characterization of a novel BH3-only pro-death protein, apolipoprotein L1 (ApoL1), that, when overexpressed, induces autophagic cell death (ACD) in a variety of cells, including those originated from normal and cancerous tissues. ApoL1 failed to induce ACD in autophagy-deficient Atg5(-/-) and Atg7(-/-) MEF cells, suggesting that ApoL1-induced cell death is indeed autophagy-dependent. In addition, a BH3 domain deletion allele of ApoL1 was unable to induce ACD, demonstrating that ApoL1 is a bona fide BH3-only pro-death protein. To further investigate regulation of ApoL1 expression, we showed that ApoL1 is inducible by interferon-gamma and tumor necrosis factor-alpha in human umbilical vein endothelial cells, suggesting that ApoL1 may play a role in cytokine-induced inflammatory response. Moreover, we observed that ApoL1 is a lipid-binding protein with high affinity for phosphatidic acid and cardiolipin and less affinity for various phosphoinositides. Functional genomics analysis identified 5 nonsynonymous single nucleotide polymorphisms (NSNPs) in the coding exons of the human ApoL1 structural gene-all the 5 NSNPs may cause deleterious alteration of ApoL1 activity. Finally, we discuss the link between ApoL1 and various human diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Apolipoprotein L1
  • Apolipoproteins / genetics
  • Apolipoproteins / metabolism*
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Autophagy*
  • BH3 Interacting Domain Death Agonist Protein / metabolism
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Humans
  • Interferon-gamma / metabolism
  • Interferon-gamma / pharmacology
  • Lipid Metabolism
  • Lipoproteins, HDL / genetics
  • Lipoproteins, HDL / metabolism*
  • Molecular Sequence Data
  • Polymorphism, Single Nucleotide
  • Schizophrenia / genetics
  • Schizophrenia / metabolism
  • Schizophrenia / pathology
  • Trypanosomiasis, African / genetics
  • Trypanosomiasis, African / metabolism
  • Trypanosomiasis, African / pathology
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology
  • Umbilical Veins / cytology
  • Umbilical Veins / drug effects
  • Umbilical Veins / metabolism


  • APOL1 protein, human
  • Apolipoprotein L1
  • Apolipoproteins
  • BH3 Interacting Domain Death Agonist Protein
  • BID protein, human
  • Lipoproteins, HDL
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma