ArticleCell reports2015
PKA Phosphorylation of NCLX Reverses Mitochondrial Calcium Overload and Depolarization, Promoting Survival of PINK1-Deficient Dopaminergic Neurons.
Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
What it found
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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.
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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.
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Who cites it
109 citing papers in PubMed, 168 citations in OpenAlex.
- Asymmetric distribution of mitochondrial CaExperimental & molecular medicine · 2026Article
- Intracellular CaInternational journal of molecular sciences · 2026Article
- Molecular mechanisms of mitochondrial CaNature communications · 2026Article
- The role of mitochondrial Na⁺/Ca²⁺ exchanger in brain cell aging.Journal of bioenergetics and biomembranes · 2026Review
- Genetic ablation of neuronal mitochondrial calcium uptake impedes Alzheimer's disease progression.The EMBO journal · 2026Article
- Mitochondrial calcium regulates lipid metabolism by modulating tethering of mitochondria to lipid droplets.The EMBO journal · 2026Article
- Nrf2 modulates cytosolic and mitochondrial calcium signal.Redox biology · 2026Article
- Loss of PINK1 causes age-dependent mitochondrial trafficking deficits in nigrostriatal dopaminergic neurons via aberrant p38 MAPK activation.NPJ Parkinson's disease · 2026Article
- Elevating levels of neuronal MCU in the hippocampus enhances mitochondrial calcium uptake and respiratory efficiency proportional to demand.bioRxiv : the preprint server for biology · 2026Article
- Molecular mechanisms of mitochondrial CabioRxiv : the preprint server for biology · 2026Article
- A central role for PINK1 in governing local mitochondrial biogenesis and degradation in neurons.Cellular and molecular life sciences : CMLS · 2026Review
- Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders.Autophagy · 2026Review
- Mitochondrial pearling: membrane biophysics, CaFrontiers in cell and developmental biology · 2026Review
- Insights into PINK1/Parkin function and dysfunction from Drosophila models.The Biochemical journal · 2025Review
- Article
- A deadly taste: linking bitter taste receptors and apoptosis.Apoptosis : an international journal on programmed cell death · 2025Review
- Altered Mitochondrial Bioenergetics and Calcium Kinetics in Young-Onset PLA2G6 Parkinson's Disease iPSCs.Journal of neurochemistry · 2025Article
- A long-lived pool of PINK1 imparts a molecular memory of depolarization-induced activity.Science advances · 2025Article
- Calcium-mediated regulation of mitophagy: implications in neurodegenerative diseases.npj metabolic health and disease · 2025Review
- The Role of Autophagy in Excitotoxicity, Synaptic Mitochondrial Stress and Neurodegeneration.Autophagy reports · 2025Article
49 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 4 countries.
Funding
Abstract
Mitochondrial Ca(2+) overload is a critical, preceding event in neuronal damage encountered during neurodegenerative and ischemic insults. We found that loss of PTEN-induced putative kinase 1 (PINK1) function, implicated in Parkinson disease, inhibits the mitochondrial Na(+)/Ca(2+) exchanger (NCLX), leading to impaired mitochondrial Ca(2+) extrusion. NCLX activity was, however, fully rescued by activation of the protein kinase A (PKA) pathway. We further show that PKA rescues NCLX activity by phosphorylating serine 258, a putative regulatory NCLX site. Remarkably, a constitutively active phosphomimetic mutant of NCLX (NCLX(S258D)) prevents mitochondrial Ca(2+) overload and mitochondrial depolarization in PINK1 knockout neurons, thereby enhancing neuronal survival. Our results identify an mitochondrial Ca(2+) transport regulatory pathway that protects against mitochondrial Ca(2+) overload. Because mitochondrial Ca(2+) dyshomeostasis is a prominent feature of multiple disorders, the link between NCLX and PKA may offer a therapeutic target.
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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.