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Editorial
. 2017 Apr;28(4):1008-1011.
doi: 10.1681/ASN.2016111262. Epub 2017 Feb 14.

Identifying the Intracellular Function of APOL1

Leslie A Bruggeman  1 , John F O'Toole  2 , John R Sedor  2   3
Affiliations
Editorial

Identifying the Intracellular Function of APOL1

Leslie A Bruggeman et al. J Am Soc Nephrol. 2017 Apr.
No abstract available

Keywords: cell death; chronic kidney disease; human genetics.

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Figures

Figure 1.
Figure 1.
Summary of APOL1 killing mechanisms associated with lysosomal and mitochondrial membrane permeabilization by intracellular, membrane-associated APOL1. (A) Trypanolysis begins with endocytosis of HDL particles containing APOL1 (red). With acidification of endosomes, the engulfed APOL1 undergoes a conformation change that results in membrane insertion, forming a pore. Acidified APOL1 can be shuttled via kinesins to mitochondria, causing mitochondrial membrane depolarization and subsequent activation of apoptotic-like death triggers, or endosomes containing APOL1 can fuse with lysosomes and cause lysosomal membrane permeabilization and osmotic swelling. (B) In yeast, fly nephrocytes, and human kidney cells, APOL1 is produced by normal biosynthetic pathways within the cell. APOL1 caused an increase in endocytic activity and reduced organelle acidification, ultimately resulting in cell hypertrophy and death. Mitochondrial membrane potential was also reduced and preceded cell death. Cytotoxicity of APOL1 was pH dependent. Although not directly examined in these reports, others have observed that APOL1 may insert into plasma membranes (dashed lines) of both trypanosomes and human kidney cells., ER, endoplasmic reticulum; Hpr, Haptoglobin-related protein.
See this image and copyright information in PMC

Comment on

  • APOL1 Renal-Risk Variants Induce Mitochondrial Dysfunction.
    Ma L, Chou JW, Snipes JA, Bharadwaj MS, Craddock AL, Cheng D, Weckerle A, Petrovic S, Hicks PJ, Hemal AK, Hawkins GA, Miller LD, Molina AJ, Langefeld CD, Murea M, Parks JS, Freedman BI. Ma L, et al. J Am Soc Nephrol. 2017 Apr;28(4):1093-1105. doi: 10.1681/ASN.2016050567. Epub 2016 Nov 7. J Am Soc Nephrol. 2017. PMID: 27821631 Free PMC article.
  • APOL1-G1 in Nephrocytes Induces Hypertrophy and Accelerates Cell Death.
    Fu Y, Zhu JY, Richman A, Zhang Y, Xie X, Das JR, Li J, Ray PE, Han Z. Fu Y, et al. J Am Soc Nephrol. 2017 Apr;28(4):1106-1116. doi: 10.1681/ASN.2016050550. Epub 2016 Nov 18. J Am Soc Nephrol. 2017. PMID: 27864430 Free PMC article.
  • APOL1-Mediated Cell Injury Involves Disruption of Conserved Trafficking Processes.
    Kruzel-Davila E, Shemer R, Ofir A, Bavli-Kertselli I, Darlyuk-Saadon I, Oren-Giladi P, Wasser WG, Magen D, Zaknoun E, Schuldiner M, Salzberg A, Kornitzer D, Marelja Z, Simons M, Skorecki K. Kruzel-Davila E, et al. J Am Soc Nephrol. 2017 Apr;28(4):1117-1130. doi: 10.1681/ASN.2016050546. Epub 2016 Nov 18. J Am Soc Nephrol. 2017. PMID: 27864431 Free PMC article.

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