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Updated: Jun 28, 2026

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy
Published on: January 31, 2025
ApoL1, a BH3-only lipid-binding protein, induces autophagic cell death
Siqin Zhaorigetu1, Guanghua Wan, Ramesh Kaini
1Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, School of Medicine, Albuquerque, New Mexico 87131-0001, USA.
Abstract:
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.
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