ArticleFrontiers in cell and developmental biology2021
Autophagy-Related LC3 Accumulation Interacted Directly With LIR Containing RIPK1 and RIPK3, Stimulating Necroptosis in Hypoxic Cardiomyocytes.
Article in Frontiers in cell and developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Necroptosis and the RIPK1-RIPK3-MLKL pathway in chronic kidney disease: mechanisms, crosstalk, and therapeutic opportunities.Renal failure · 2026Review
- Rictor/mTORC2 signaling pathway protects endogenous neural stem cells to promote recovery after spinal cord injury.Neural regeneration research · 2026Article
- Cutting edge: ESCRT-mediated phagophore closure in mammals.The Biochemical journal · 2026Review
- Lys-ing the Resistance: Targeting Lysosomes to Overcome Chemoresistance in Ovarian Cancer.Current oncology reports · 2026Review
- Design of CellProfiler-Based Pipelines Enabling the Attribution of Molecular Stress Markers to Specific Tissue and Subcellular Compartments of the Colonic Mucosa.Cellular and molecular gastroenterology and hepatology · 2026Article
- Autophagy-Induced Microglial Death Contributes to Neuroinflammation in Acute Optic Nerve Injury.Investigative ophthalmology & visual science · 2025Article
- Obtain substance of anti-glioblastoma from Erigeron breviscapus through fragment-based target research (FBTR): An efficient strategy for pharmacology investigation and optimization of natural products.Journal of pharmaceutical analysis · 2025Article
- Heat shock protein A1 inhibits the replication of foot-and-mouth disease virus by degrading viral RNA polymerase 3D through chaperone-mediated autophagy.Journal of virology · 2025Article
- The inducible role of autophagy in cell death: emerging evidence and future perspectives.Cell communication and signaling : CCS · 2025Review
- Cigarette smoke exposure triggers dendritic cell-derived exosome-mediated Th17 and Treg polarization through an autophagy- and necroptosis-associated SIRT1-dependent mechanism in vitro.Frontiers in immunology · 2025Article
- Unveiling the physiological impact of ESCRT-dependent autophagosome closure by targeting the VPS37A ubiquitin E2 variant-like domain.Cell reports · 2024Article
- The assembly and activation of the PANoptosome promote porcine granulosa cell programmed cell death during follicular atresia.Journal of animal science and biotechnology · 2024Article
- mTORC1 hyperactivation and resultant suppression of macroautophagy contribute to the induction of cardiomyocyte necroptosis by catecholamine surges.Physiological reports · 2024Article
- Mitophagy associated self-degradation of phosphorylated MAP4 guarantees the migration and proliferation responses of keratinocytes to hypoxia.Cell death discovery · 2023Article
- Progress in study on the final executor of necroptosis MLKL and its inhibitors.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- Autophagy and necroptosis in cisplatin-induced acute kidney injury: Recent advances regarding their role and therapeutic potential.Frontiers in pharmacology · 2023Review
- Merits of hiPSC-Derived Cardiomyocytes for In Vitro Research and Testing Drug Toxicity.Biomedicines · 2022Article
- RIPK1-RIPK3 mediates myocardial fibrosis in type 2 diabetes mellitus by impairing autophagic flux of cardiac fibroblasts.Cell death & disease · 2022Article
- Comprehensive Characterization of Necroptosis-Related lncRNAs in Bladder Cancer Identifies a Novel Signature for Prognosis Prediction.Disease markers · 2022Article
- The multifunctional roles of autophagy in the innate immune response: Implications for regulation of transplantation rejection.Frontiers in cell and developmental biology · 2022Review
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The exact relationships and detailed mechanisms between autophagy and necroptosis remain obscure. Here, we demonstrated the link between accumulated autophagosome and necroptosis by intervening with autophagic flux. We first confirmed that the LC3 interacting region (LIR) domain is present in the protein sequences of RIPK1 and RIPK3. Mutual effects among LC3, RIPK1, and RIPK3 have been identified in myocardium and cardiomyocytes. Direct LC3-RIPK1 and LC3-RIPK3 interactions were confirmed by pull-down assays, and their interactions were deleted after LIR domain mutation. Moreover, after disrupting autophagic flux under normoxia with bafilomycin A1 treatment, or with LC3 or ATG5 overexpression adenovirus, RIPK1, RIPK3, p-RIPK3, and p-MLKL levels increased, suggesting necroptosis activation. Severe disruptions in autophagic flux were observed under hypoxia and bafilomycin A1 co-treated cardiomyocytes and myocardium and led to more significant activation of necroptosis. Conversely, after alleviating hypoxia-induced autophagic flux impairment with LC3 or ATG5 knockdown adenovirus, the effects of hypoxia on RIPK1 and RIPK3 levels were reduced, which resulted in decreased p-RIPK3 and p-MLKL. Furthermore, necroptosis was inhibited by siRNAs against RIPK1 and RIPK3 under hypoxia or normoxia. Based on our results, LIR domain mediated LC3-RIPK1 and LC3-RIPK3 interaction. Besides, autophagosome accumulation under hypoxia lead to necrosome formation and, in turn, necroptosis, while when autophagic flux was uninterrupted, RIPK1 and RIPK3 were cleared through an autophagy-related pathway which inhibited necroptosis. These findings provide novel insights for the role of LC3 in regulating cardiomyocyte necroptosis, indicating its therapeutic potential in the prevention and treatment of hypoxic myocardial injury and other hypoxia-related diseases.
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