ArticleCell death and differentiation2011
Mitochondrially localized PKA reverses mitochondrial pathology and dysfunction in a cellular model of Parkinson's disease.
Article in Cell death and differentiation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 2 of them syntheses that pooled it.
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Who cites it
100 citing papers in PubMed, 2 syntheses or guidelines pooled it, 140 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- PRKAR2A/RIIα as a candidate spatial cAMP-PKA signal router in triple-negative breast cancer metastasis: evidence boundaries, competing models and decisive experiments.Molecular biology reports · 2026Review
- Postbiotic metabolites fromExperimental and therapeutic medicine · 2026Article
- PKA activation rescues myocardial injury elicited by silica nanoparticles through improving oxidative stress, mitochondrial health, and copper homeostasis.Materials today. Bio · 2026Article
- Cerebellar deep brain stimulation rescues Purkinje cell mitochondrial density in a genetic mouse model of cerebellar ataxia.Brain research bulletin · 2026Article
- Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders.Autophagy · 2026Review
- Insights into PINK1/Parkin function and dysfunction from Drosophila models.The Biochemical journal · 2025Review
- Aberrant phase separation of two PKA RIβ neurological disorder mutants leads to mechanistically distinct signaling deficits.Cell reports · 2025Article
- The Mitochondrial Foundations of Parkinson's Disease: Therapeutic Implications.Aging and disease · 2025Review
- Neuroprotective Role of Cyclic AMP Signaling in Dopaminergic Degeneration Induced by a Parkinson's Disease Toxin, Rotenone.NeuroSci · 2025Article
- AKAP1/PKA-mediated GRP75 phosphorylation at mitochondria-associated endoplasmic reticulum membranes protects cancer cells against ferroptosis.Cell death and differentiation · 2025Article
- Phosphodiesterase inhibition and Gucy2C activation enhance tyrosine hydroxylase Ser40 phosphorylation and improve 6-hydroxydopamine-induced motor deficits.Cell & bioscience · 2024Article
- Article
- Effect of ferric citrate on hippocampal iron accumulation and widespread molecular alterations associated with cognitive disorder in an ovariectomized mice model.CNS neuroscience & therapeutics · 2024Article
- Unraveling the mechanistic interplay of mediators orchestrating the neuroprotective potential of harmine.Pharmacological reports : PR · 2024Review
- Research progress on intranasal treatment for Parkinson's disease.Neuroprotection (Chichester, England) · 2024Review
- Novel insights into D-Pinitol based therapies: a link between tau hyperphosphorylation and insulin resistance.Neural regeneration research · 2024Review
- Engineered Selenium/Human Serum Albumin Nanoparticles for Efficient Targeted Treatment of Parkinson's Disease via Oral Gavage.ACS nano · 2023Article
- Brain-derived neurotrophic factor protects neurons by stimulating mitochondrial function through protein kinase A.Journal of neurochemistry · 2023Article
40 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Mutations in PTEN-induced kinase 1 (PINK1) are associated with a familial syndrome related to Parkinson's disease (PD). We previously reported that stable neuroblastoma SH-SY5Y cell lines with reduced expression of endogenous PINK1 exhibit mitochondrial fragmentation, increased mitochondria-derived superoxide, induction of compensatory macroautophagy/mitophagy and a low level of ongoing cell death. In this study, we investigated the ability of protein kinase A (PKA) to confer protection in this model, focusing on its subcellular targeting. Either: (1) treatment with pharmacological PKA activators; (2) transient expression of a constitutively active form of mitochondria-targeted PKA; or (3) transient expression of wild-type A kinase anchoring protein 1 (AKAP1), a scaffold that targets endogenous PKA to mitochondria, reversed each of the phenotypes attributed to loss of PINK1 in SH-SY5Y cells, and rescued parameters of mitochondrial respiratory dysfunction. Mitochondrial and lysosomal changes in primary cortical neurons derived from PINK1 knockout mice or subjected to PINK1 RNAi were also reversed by the activation of PKA. PKA phosphorylates the rat dynamin-related protein 1 isoform 1 (Drp1) at serine 656 (homologous to human serine 637), inhibiting its pro-fission function. Mimicking phosphorylation of Drp1 recapitulated many of the protective effects of AKAP1/PKA. These data indicate that redirecting endogenous PKA to mitochondria can compensate for deficiencies in PINK1 function, highlighting the importance of compartmentalized signaling networks in mitochondrial quality control.
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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.