ArticleCell death and differentiation2018
Extracellular anti-angiogenic proteins augment an endosomal protein trafficking pathway to reach mitochondria and execute apoptosis in HUVECs.
Article in Cell death and differentiation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
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- Short-term Physical Activity Reduces Metabolic-associated Steatohepatitis by Promoting the Degradation of Branched-chain Amino Acids in Skeletal Muscle.Journal of clinical and translational hepatology · 2025Article
- Phosphoinositide signalling in cell motility and adhesion.Nature cell biology · 2025Review
- Phosphoinositide signaling at the cytoskeleton in the regulation of cell dynamics.Cell death & disease · 2025Review
- Mitophagy in perioperative neurocognitive disorder: mechanisms and therapeutic strategies.European journal of medical research · 2025Review
- PDGFR-α shRNA-polyplex for uveal melanoma treatment via EMT mediated vasculogenic mimicry interfering.Journal of nanobiotechnology · 2024Article
- Small RNA-big impact: exosomal miRNAs in mitochondrial dysfunction in various diseases.RNA biology · 2024Review
- Delivery of low-density lipoprotein from endocytic carriers to mitochondria supports steroidogenesis.Nature cell biology · 2023Article
- The Angiogenesis Inhibitor Isthmin-1 (ISM1) Is Overexpressed in Experimental Models of Glomerulopathy and Impairs the Viability of Podocytes.International journal of molecular sciences · 2023Article
- Poison cassette exon splicing of SRSF6 regulates nuclear speckle dispersal and the response to hypoxia.Nucleic acids research · 2023Article
- ISM1 protects lung homeostasis via cell-surface GRP78-mediated alveolar macrophage apoptosis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The effect of extracellular vesicles on the regulation of mitochondria under hypoxia.Cell death & disease · 2021Review
- Development of Extracellular Vesicle Therapeutics: Challenges, Considerations, and Opportunities.Frontiers in cell and developmental biology · 2021Review
- Assessing In Situ Phosphoinositide-Protein Interactions Through Fluorescence Proximity Ligation Assay in Cultured Cells.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Sodium Hydrogen Exchanger Regulatory Factor-1 (NHERF1) Regulates Fetal Membrane Inflammation.International journal of molecular sciences · 2020Article
- Article
- Endolysosomal Targeting of Mitochondria Is Integral to BAX-Mediated Mitochondrial Permeabilization during Apoptosis Signaling.Developmental cell · 2020Article
- Fucosterol Suppresses the Progression of Human Ovarian Cancer by Inducing Mitochondrial Dysfunction and Endoplasmic Reticulum Stress.Marine drugs · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Classic endocytosis destinations include the recycling endosome returning to the plasma membrane or the late endosome (LE) merging with lysosomes for cargo degradation. However, the anti-angiogenic proteins angiostatin and isthmin, are endocytosed and trafficked to mitochondria (Mito) to execute apoptosis of endothelial cells. How these extracellular proteins reach mitochondria remains a mystery. Through confocal and super-resolution fluorescent microscopy, we demonstrate that angiostatin and isthmin are trafficked to mitochondria through the interaction between LE and Mito. Using purified organelles, the LE-Mito interaction is confirmed through in vitro lipid-fusion assay, as well as single vesicle total internal reflection fluorescent microscopy. LE-Mito interaction enables the transfer of not only lipids but also proteins from LE to Mito. Angiostatin and isthmin augment this endosomal protein trafficking pathway and make use of it to reach mitochondria to execute apoptosis. Cell fractionation and biochemical analysis identified that the cytosolic scaffold protein Na+/H+ exchanger regulatory factor 1 (NHERF1) associated with LE and the t-SNARE protein synaptosome-associated protein 25 kDa (SNAP25) associated with Mito form an interaction complex to facilitate LE-Mito interaction. Proximity ligation assay coupled with fluorescent microscopy showed that both NHERF1 and SNAP25 are located at the contacting face between LE and Mito. RNAi knockdown of either NHERF1 or SNAP25 suppressed not only the mitochondrial trafficking of angiostatin and isthmin but also their anti-angiogenic and pro-apoptotic functions. Hence, this study reveals a previously unrealized endosomal protein trafficking pathway from LE to Mito that allows extracellular proteins to reach mitochondria and execute apoptosis.
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