ArticleJournal of lipid research2012
Phosphatidic acid mediates the targeting of tBid to induce lysosomal membrane permeabilization and apoptosis.
Article in Journal of lipid research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 47 citations in OpenAlex.
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- Regulation of Cell Proliferation and Migration by Extracellular Phosphatidic Acid.Biomedicines · 2026Review
- Cell-Based Metabolomics Approach for Anticipating and Investigating Cytotoxicity of Gold Nanorods.Foods (Basel, Switzerland) · 2022Article
- Apoptotic stress-induced FGF signalling promotes non-cell autonomous resistance to cell death.Nature communications · 2021Article
- The function of apolipoproteins L (APOLs): relevance for kidney disease, neurotransmission disorders, cancer and viral infection.The FEBS journal · 2021Review
- Multi-Omics Prognostic Signatures Based on Lipid Metabolism for Colorectal Cancer.Frontiers in cell and developmental biology · 2021Article
- N-Methyl-D-Aspartate Receptor Signaling-Protein Kinases Crosstalk in Cerebral Ischemia.Advances in experimental medicine and biology · 2021Article
- The Importance of mTOR Trafficking for Human Skeletal Muscle Translational Control.Exercise and sport sciences reviews · 2019Review
- Loss of lipin 1-mediated phosphatidic acid phosphohydrolase activity in muscle leads to skeletal myopathy in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Neuronal Cell Death.Physiological reviews · 2018Review
- Article
- ESeroS-GS Protects Neuronal Cells from Oxidative Stress by Stabilizing Lysosomes.Molecules (Basel, Switzerland) · 2016Article
- Mechanosensitive Molecular Networks Involved in Transducing Resistance Exercise-Signals into Muscle Protein Accretion.Frontiers in physiology · 2016Review
- Mcl-1 is vital for neutrophil survival.Immunologic research · 2015Review
- Lipid metabolism, apoptosis and cancer therapy.International journal of molecular sciences · 2015Review
- The mechanical activation of mTOR signaling: an emerging role for late endosome/lysosomal targeting.Journal of muscle research and cell motility · 2014Review
- The role of diacylglycerol kinase ζ and phosphatidic acid in the mechanical activation of mammalian target of rapamycin (mTOR) signaling and skeletal muscle hypertrophy.The Journal of biological chemistry · 2014Article
- Lysosomal chymotrypsin induces mitochondrial fission in apoptotic cells by proteolytic activation of calcineurin.Protein & cell · 2014Article
- Eccentric contractions increase the phosphorylation of tuberous sclerosis complex-2 (TSC2) and alter the targeting of TSC2 and the mechanistic target of rapamycin to the lysosome.The Journal of physiology · 2013Article
- HSP70 inhibition by 2-phenylethynesulfonamide induces lysosomal cathepsin D release and immunogenic cell death in primary effusion lymphoma.Cell death & disease · 2013Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Upon apoptotic stimuli, lysosomal proteases, including cathepsins and chymotrypsin, are released into cytosol due to lysosomal membrane permeabilization (LMP), where they trigger apoptosis via the lysosomal-mitochondrial pathway of apoptosis. Herein, the mechanism of LMP was investigated. We found that caspase 8-cleaved Bid (tBid) could result in LMP directly. Although Bax or Bak might modestly enhance tBid-triggered LMP, they are not necessary for LMP. To study this further, large unilamellar vesicles (LUVs), model membranes mimicking the lipid constitution of lysosomes, were used to reconstitute the membrane permeabilization process in vitro. We found that phosphatidic acid (PA), one of the major acidic phospholipids found in lysosome membrane, is essential for tBid-induced LMP. PA facilitates the insertion of tBid deeply into lipid bilayers, where it undergoes homo-oligomerization and triggers the formation of highly curved nonbilayer lipid phases. These events induce LMP via pore formation mechanisms because encapsulated fluorescein-conjugated dextran (FD)-20 was released more significantly than FD-70 or FD-250 from LUVs due to its smaller molecular size. On the basis of these data, we proposed tBid-PA interactions in the lysosomal membranes form lipidic pores and result in LMP. We further noted that chymotrypsin-cleaved Bid is more potent than tBid at binding to PA, inserting into the lipid bilayer, and promoting LMP. This amplification mechanism likely contributes to the culmination of apoptotic signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.