ArticleNature structural & molecular biology2024
Control of mitophagy initiation and progression by the TBK1 adaptors NAP1 and SINTBAD.
Article in Nature structural & molecular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Nitric oxide signaling and mitophagy in Parkinson's disease: implications for aerobic exercise-related neuroprotection.Medical gas research · 2027Review
- The role of E3 ubiquitin ligases in selective types of macroautophagy.EMBO reports · 2026Review
- Ubiquitination-dependent regulation of ferroptosis in ischemic heart and brain.Redox biology · 2026Review
- NAP1 switches from an activator to a limiter of interferon induction by trapping TBK1 in condensates.Nature communications · 2026Article
- Regulation and roles of mammalian mitophagy.Nature reviews. Molecular cell biology · 2026Review
- The Role of Inflammation and Immunity in Cardiovascular Disease: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- Germline regulation of tumor evolutionary dynamics shapes multiple myeloma progression.bioRxiv : the preprint server for biology · 2026Article
- Phosphorylation tunes p62 condensates to drive autophagic degradation of ubiquitinated proteins.The EMBO journal · 2026Article
- USP1 promotes hepatocellular carcinoma progression by modulating mitophagy via stabilizing MCM3 to regulate the Keap1-Nrf2 axis.iScience · 2026Article
- Review
- Cytosolic nucleic acid sensing triggers type I interferon activation via the Hippo kinase LATS1.The Journal of biological chemistry · 2026Article
- TANK-binding kinase 1 protects against MASH progression via mitochondrial quality control.Experimental & molecular medicine · 2026Article
- Mitophagy and Ubiquitination Coordinate Context-Specific Mitochondrial Quality Control and EMT/MET Plasticity to Drive Cancer Cell Invasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- TBK1 Induces the Formation of Optineurin Filaments That Condensate with Polyubiquitin and LC3 for Cargo Sequestration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Human papillomavirus E7 inhibits immune responses in keratinocytes by activating HTRA1‑mediated mitophagy.International journal of molecular medicine · 2026Article
- Minding the gates: dual cell-autonomous and non-cell-autonomous mechanisms of TBK1 in ALS/FTD.Frontiers in neuroscience · 2026Review
- Therapeutic Promise of Mitophagy in Cancer: Advancing from Small-Molecule Regulation to Nanotechnology-Enhanced Targeting Therapy.Theranostics · 2026Review
- Mitochondrial quality control: a new mechanism for antiviral therapy.Frontiers in immunology · 2026Review
- Exploring TANK-Binding Kinase 1 in Amyotrophic Lateral Sclerosis: From Structural Mechanisms to Machine Learning-Guided Therapeutics.Life (Basel, Switzerland) · 2025Review
- Tank-Binding Kinase 1 protects against MASH progression via mitochondrial quality control.Research square · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitophagy preserves overall mitochondrial fitness by selectively targeting damaged mitochondria for degradation. The regulatory mechanisms that prevent PTEN-induced putative kinase 1 (PINK1) and E3 ubiquitin ligase Parkin (PINK1/Parkin)-dependent mitophagy and other selective autophagy pathways from overreacting while ensuring swift progression once initiated are largely elusive. Here, we demonstrate how the TBK1 (TANK-binding kinase 1) adaptors NAP1 (NAK-associated protein 1) and SINTBAD (similar to NAP1 TBK1 adaptor) restrict the initiation of OPTN (optineurin)-driven mitophagy by competing with OPTN for TBK1. Conversely, they promote the progression of nuclear dot protein 52 (NDP52)-driven mitophagy by recruiting TBK1 to NDP52 and stabilizing its interaction with FIP200. Notably, OPTN emerges as the primary recruiter of TBK1 during mitophagy initiation, which in return boosts NDP52-mediated mitophagy. Our results thus define NAP1 and SINTBAD as cargo receptor rheostats, elevating the threshold for mitophagy initiation by OPTN while promoting the progression of the pathway once set in motion by supporting NDP52. These findings shed light on the cellular strategy to prevent pathway hyperactivity while still ensuring efficient progression.
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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.