ArticleAutophagy2016
Hypoxia promotes noncanonical autophagy in nucleus pulposus cells independent of MTOR and HIF1A signaling.
Article in Autophagy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 107 citations in OpenAlex.
- Review
- Current research on the role of HIF in intervertebral disc degeneration.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Review
- Membrane-camouflaged nanoparticle alleviates intervertebral disc degeneration via oxidative stress suppression and autophagy activation.Materials today. Bio · 2026Article
- ABCG2-autophagy regulatory axis in cancer stem cells: implication in cancer metastasis, recurrence and chemotherapy resistance.Cell communication and signaling : CCS · 2026Review
- Stress-response exhaustion in intervertebral disc degeneration.Frontiers in cell and developmental biology · 2026Review
- Hypoxic Status in COPD and ARDS Patients: Impact on Lipid Signature.International journal of molecular sciences · 2025Article
- The loss of OPA1 accelerates intervertebral disc degeneration and osteoarthritis in aged mice.Nature communications · 2025Article
- PTB Regulates Keloid Fibroblast Migration and Proliferation Through Autophagy.Aesthetic plastic surgery · 2025Article
- Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Alleviate Nuclear Pulposus Cells Degeneration Through the miR-145a-5p/USP31/HIF-1α Signaling Pathway.Stem cell reviews and reports · 2024Article
- Piezo1 channel exaggerates ferroptosis of nucleus pulposus cells by mediating mechanical stress-induced iron influx.Bone research · 2024Article
- HIF-1α-PPARγ-mTORC1 signaling pathway-mediated autophagy induces inflammatory response in pancreatic cells in rats with hyperlipidemic acute pancreatitis.Molecular biology reports · 2023Article
- Thrombotic Alterations under Perinatal Hypoxic Conditions: HIF and Other Hypoxic Markers.International journal of molecular sciences · 2023Review
- Article
- Intervertebral disc cell fate during aging and degeneration: apoptosis, senescence, and autophagy.North American Spine Society journal · 2023Article
- G3BP1 coordinates lysophagy activity to protect against compression-induced cell ferroptosis during intervertebral disc degeneration.Cell proliferation · 2023Article
- Circular RNA and intervertebral disc degeneration: unravelling mechanisms and implications.Frontiers in molecular biosciences · 2023Review
- Conditional Deletion of HIF-2α in Mouse Nucleus Pulposus Reduces Fibrosis and Provides Mild and Transient Protection From Age-Dependent Structural Changes in Intervertebral Disc.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Knockdown of triggering receptor expressed on myeloid cells 1 (TREM1) inhibits endoplasmic reticulum stress and reduces extracellular matrix degradation and the apoptosis of human nucleus pulposus cells.Experimental and therapeutic medicine · 2022Article
- Exhausted local lactate accumulation via injectable nanozyme-functionalized hydrogel microsphere for inflammation relief and tissue regeneration.Bioactive materials · 2022Article
- Ganoderic Acid A Attenuates IL-1β-Induced Inflammation in Human Nucleus Pulposus Cells Through Inhibiting the NF-κB Pathway.Inflammation · 2022Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Nucleus pulposus (NP) cells reside in the avascular and hypoxic microenvironment of intervertebral discs. Importantly, many activities related to survival and function of NP cells are controlled by the HIF-family of transcription factors. We hypothesize that NP cells adapt to their hypoxic niche through modulation of macroautophagy/autophagy. In various cell types, hypoxia induces autophagy in a HIF1A-dependent fashion; however, little is known about hypoxic regulation of autophagy in NP cells. Hypoxia increases the number of autophagosomes as seen by TEM analysis and LC3-positive puncta in NP cells. Hypoxic induction of autophagy was also demonstrated by a significantly higher number of autophagosomes and smaller change in autolysosomes in NP cells expressing tandem-mCherry-EGFP-LC3B. Increased LC3-II levels were not accompanied by a concomitant increase in BECN1 or the ATG12-ATG5 complex. In addition, ULK1 phosphorylation at Ser757 and Ser777 responsive to MTOR and AMPK, respectively, was not affected in hypoxia. Interestingly, when MTOR activity was inhibited by rapamycin or Torin1, LC3-II levels did not change, suggesting a novel MTOR-independent regulation. Noteworthy, while silencing of HIF1A affected hypoxic induction of BNIP3, it did not affect LC3-II levels, indicating hypoxia-induced autophagy is HIF1-independent. Importantly, there was no change in the number of LC3-positive autophagosomes in NP-specific Hif1a null mice. Finally, inhibition of autophagic flux did not affect the glycolytic metabolism of NP cells, suggesting a possible nonmetabolic role of autophagy. Taken together, our study for the first time shows that NP cells regulate autophagy in a noncanonical fashion independent of MTOR and HIF1A 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.