ArticleNPJ Parkinson's disease2019
PINK1 phosphorylates ubiquitin predominantly in astrocytes.
Article in NPJ Parkinson's disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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
38 citing papers in PubMed, 45 citations in OpenAlex.
- Nitric oxide signaling and mitophagy in Parkinson's disease: implications for aerobic exercise-related neuroprotection.Medical gas research · 2027Review
- Mitophagy in neuronal health and disease: from mechanisms to neurodegeneration.The Journal of clinical investigation · 2026Review
- Astrocytes orchestrate neuroprotection and pathogenesis via bidirectional neuronal interactions in Parkinson's disease.Journal of physiology and biochemistry · 2026Review
- PINK1 loss in astrocytes triggers inflammatory dysfunction and neuronal death.bioRxiv : the preprint server for biology · 2026Article
- The role of phospho-ubiquitin in mitochondrial health and diseases.The Journal of biological chemistry · 2026Review
- Modeling CLN3 Batten disease in astrocytes reveals alterations in mitochondria homeostasis, fatty acid metabolism and oxidative stress response.Journal of biomedical science · 2026Article
- PINK1/Parkin-dependent mitophagy mediates astrocytic inflammatory responses to mitochondrial damage.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial damage triggers the concerted degradation of negative regulators of neuronal autophagy.Nature communications · 2025Article
- Mitophagy's impacts on cancer and neurodegenerative diseases: implications for future therapies.Journal of hematology & oncology · 2025Review
- Targeting mitophagy in neurodegenerative diseases.Nature reviews. Drug discovery · 2025Review
- Mechanisms of astrocyte aging in reactivity and disease.Molecular neurodegeneration · 2025Review
- Exercise regulates mitophagy to alleviate parkinsonian neurodegeneration.Frontiers in aging neuroscience · 2025Review
- Pathogenic synergy: dysfunctional mitochondria and neuroinflammation in neurodegenerative diseases associated with aging.Frontiers in aging · 2025Review
- Mitochondrial dysfunction in Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- In and out: Benchmarking in vitro, in vivo, ex vivo, and xenografting approaches for an integrative brain disease modeling pipeline.Stem cell reports · 2024Review
- Pathogenesis of Parkinson's disease: from hints from monogenic familial PD to biomarkers.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Article
- Gene Expression at the Tripartite Synapse: Bridging the Gap Between Neurons and Astrocytes.Advances in neurobiology · 2024Review
- PJA1 mediates the effects of astrocytic GPR30 on learning and memory in female mice.The Journal of clinical investigation · 2023Article
- Damaged mitochondria recruit the effector NEMO to activate NF-κB signaling.Molecular cell · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Loss-of-function mutations in PINK1 are causally linked to recessively inherited Parkinson's disease (PD), with marked loss of dopaminergic neurons in the substantia nigra that are required for normal movement. PINK1 is a nuclear-encoded mitochondrial-targeted kinase that phosphorylates a conserved serine at amino acid 65 (pS65) in ubiquitin as well as Parkin, another gene with loss-of-function mutations linked to recessive parkinsonism. The steady-state levels of PINK1 protein are very low, even in cells that express PINK1, because PINK1 is normally targeted for degradation after mitochondrial import by a process that is dependent upon mitochondrial membrane potential. Dissipation of the mitochondrial membrane potential with ionophores, such as CCCP and valinomycin, causes the accumulation of PINK1 on the outer mitochondrial membrane, a marked increase of pS65-ubiquitin and the recruitment of Parkin, which targets dysfunctional mitochondria for degradation by autophagy. While the high penetrance of PINK1 mutations establish its critical function for maintaining neurons, the activity of PINK1 in primary neurons has been difficult to detect. Mounting evidence implicates non-neuronal cells, including astrocytes and microglia, in the pathogenesis of both idiopathic and inherited PD. Herein we used both western analysis and immunofluorescence of pS65-ubiquitin to directly compare the activity of PINK1 in primary neurons, astrocytes, microglia, and oligodendrocyte progenitor cells cultured from the brains of wild-type (WT) and PINK1 knockout (KO) rat pups. Our findings that PINK1-dependent ubiquitin phosphorylation is predominantly in astrocytes supports increased priority for research on the function of PINK1 in astrocytes and the contribution of astrocyte dysfunction to PD pathogenesis.
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.