ArticleThe Journal of biological chemistry2013
Two pore channel 2 (TPC2) inhibits autophagosomal-lysosomal fusion by alkalinizing lysosomal pH.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 49 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 93 citations in OpenAlex.
- Targeting macroautophagy to combat neurodegenerative disease: strategies and considerations.Autophagy reports · 2025Review
- Loss of two-pore channel 2 enhances CD8+ T cell cytotoxicity and directly impairs tumour growth via MAPK axis in HCC.Frontiers in immunology · 2025Article
- Regulation of autophagy by perilysosomal calcium: a new player in β-cell lipotoxicity.Experimental & molecular medicine · 2024Review
- NAADP-Mediated CaHandbook of experimental pharmacology · 2023Article
- Quantitative phosphoproteomic analyses identify STK11IP as a lysosome-specific substrate of mTORC1 that regulates lysosomal acidification.Nature communications · 2022Article
- The ins and outs of virus trafficking through acidic CaCell calcium · 2022Review
- Article
- NAADP-dependent CaCell calcium · 2018Article
- The Outcome of theJournal of immunology (Baltimore, Md. : 1950) · 2018Article
- Ion channels in the regulation of autophagy.Autophagy · 2018Review
- NAD and the aging process: Role in life, death and everything in between.Molecular and cellular endocrinology · 2017Review
- The human two-pore channel 1 is modulated by cytosolic and luminal calcium.Scientific reports · 2017Article
- Autophagy regulates UBC9 levels during viral-mediated tumorigenesis.PLoS pathogens · 2017Article
- TMEM175 deficiency impairs lysosomal and mitochondrial function and increases α-synuclein aggregation.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Article
- Two-pore channels (TPCs): Novel voltage-gated ion channels with pleiotropic functions.Channels (Austin, Tex.) · 2017Review
- Two-Pore Channels: Catalyzers of Endolysosomal Transport and Function.Frontiers in pharmacology · 2017Review
- IPFrontiers in oncology · 2017Review
- Live-cell Microscopy and Fluorescence-based Measurement of Luminal pH in Intracellular Organelles.Frontiers in cell and developmental biology · 2017Article
- Metabolic alterations derived from absence of Two-Pore Channel 1 at cardiac level.Journal of biosciences · 2016Article
Corrections and comments
- Retraction · 2017-06-26Ethical Violations by Author · Falsification/Fabrication of Image · Investigation by Journal/Publisher · Manipulation of Images · · Yingying Lu admitted to image manipulations
- Retracted
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy is an evolutionarily conserved lysosomal degradation pathway, yet the underlying mechanisms remain poorly understood. Nicotinic acid adenine dinucleotide phosphate (NAADP), one of the most potent Ca(2+) mobilizing messengers, elicits Ca(2+) release from lysosomes via the two pore channel 2 (TPC2) in many cell types. Here we found that overexpression of TPC2 in HeLa or mouse embryonic stem cells inhibited autophagosomal-lysosomal fusion, thereby resulting in the accumulation of autophagosomes. Treatment of TPC2 expressing cells with a cell permeant-NAADP agonist, NAADP-AM, further induced autophagosome accumulation. On the other hand, TPC2 knockdown or treatment of cells with Ned-19, a NAADP antagonist, markedly decreased the accumulation of autophagosomes. TPC2-induced accumulation of autophagosomes was also markedly blocked by ATG5 knockdown. Interestingly, inhibiting mTOR activity failed to increase TPC2-induced autophagosome accumulation. Instead, we found that overexpression of TPC2 alkalinized lysosomal pH, and lysosomal re-acidification abolished TPC2-induced autophagosome accumulation. In addition, TPC2 overexpression had no effect on general endosomal-lysosomal degradation but prevented the recruitment of Rab-7 to autophagosomes. Taken together, our data demonstrate that TPC2/NAADP/Ca(2+) signaling alkalinizes lysosomal pH to specifically inhibit the later stage of basal autophagy progression.
Indexed as
Identifiers
What OpenQuestion holds
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.