ArticleProtein & cell2013
ULK1 and JNK are involved in mitophagy incurred by LRRK2 G2019S expression.
Article in Protein & cell, 2013. 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, 40 citations in OpenAlex.
- Cell Death in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- Mitochondrial Dysfunction in Neurodegenerative Diseases: Mechanisms and Corresponding Therapeutic Strategies.Biomedicines · 2025Review
- Loss of LRRK2 activity induces cytoskeleton defects and oxidative stress during porcine oocyte maturation.Cell communication and signaling : CCS · 2025Article
- Spatiotemporal crosstalk among mitochondrial dynamics, NLRP3 inflammasome activation, and histone lactylation drivesFrontiers in cellular neuroscience · 2025Review
- Chaperone-mediated autophagy in neurodegenerative diseases: mechanisms and therapy.Molecular and cellular biochemistry · 2023Review
- Mitochondrial Control in Inflammatory Gastrointestinal Diseases.International journal of molecular sciences · 2022Review
- Autophagy and Its Association with Genetic Mutations in Parkinson Disease.Medical science monitor : international medical journal of experimental and clinical research · 2022Review
- The parkinsonian LRRK2 R1441G mutation shows macroautophagy-mitophagy dysregulation concomitant with endoplasmic reticulum stress.Cell biology and toxicology · 2022Article
- Mitophagy, a Form of Selective Autophagy, Plays an Essential Role in Mitochondrial Dynamics of Parkinson's Disease.Cellular and molecular neurobiology · 2022Review
- TRK-fused gene (TFG) regulates ULK1 stability via TRAF3-mediated ubiquitination and protects macrophages from LPS-induced pyroptosis.Cell death & disease · 2022Article
- The Cross-Links of Endoplasmic Reticulum Stress, Autophagy, and Neurodegeneration in Parkinson's Disease.Frontiers in aging neuroscience · 2021Review
- A pan-cancer assessment of alterations of the kinase domain of ULK1, an upstream regulator of autophagy.Scientific reports · 2020Article
- Autophagy in Parkinson's Disease.Journal of molecular biology · 2020Review
- Article
- Emerging views of mitophagy in immunity and autoimmune diseases.Autophagy · 2020Article
- Mechanisms and roles of mitophagy in neurodegenerative diseases.CNS neuroscience & therapeutics · 2019Review
- Multiple pathways for mitophagy: A neurodegenerative conundrum for Parkinson's disease.Neuroscience letters · 2019Review
- Mechanisms of selective autophagy and mitophagy: Implications for neurodegenerative diseases.Neurobiology of disease · 2019Review
- AMPK: guardian of metabolism and mitochondrial homeostasis.Nature reviews. Molecular cell biology · 2018Review
- Hallmarks of Aging: An Autophagic Perspective.Frontiers in endocrinology · 2018Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in LR RK2 (Leucine rich repeat kinase 2) are a major cause of Parkinson's disease (PD). We and others reported recently that expression of the pathogenic gainof-function mutant form of LRRK2, LRRK2 G2019S, induces mitochondrial fission in neurons through DLP1. Here we provide evidence that expression of LRRK2 G2019S stimulates mitochondria loss or mitophagy. We have characterized several LRRK2 interacting proteins and found that LRRK2 interacts with ULK1 which plays an essential role in autophagy. Knockdown of either ULK1 or DLP1 expression with shRNAs suppresses LRRK2 G2019S expression-induced mitochondrial clearance, suggesting that LRRK2 G2019S expression induces mitochondrial fission through DLP1 followed by mitophagy via an ULK1 dependent pathway. In addition to ULK1, we found that LRRK2 interacts with the endogenous MKK4/7, JIP3 and coordinates with them in the activation of JNK signaling. Interestingly, LRRK2 G2019S-induced loss of mitochondria can also be suppressed by 3 different JNK inhibitors, implying the involvement of the JNK pathway in the pathogenic mechanism of mutated LRRK2. Thus our findings may provide an insight into the complicated pathogenesis of PD as well as some clues to the development of novel therapeutic strategies.
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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.