ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
Strong calcium entry activates mitochondrial superoxide generation, upregulating kinase signaling in hippocampal neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 139 citations in OpenAlex.
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- Association of Apolipoprotein E4-related Microvascular Disease in the Alzheimer's Disease Hippocampal CA1 Stratum Radiatum.Neuroscience · 2023Article
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- Activity-regulated growth of motoneurons at the neuromuscular junction is mediated by NADPH oxidases.Frontiers in cellular neuroscience · 2022Article
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- Overshooting Subcellular Redox-Responses in Rett-Mouse Hippocampus during Neurotransmitter Stimulation.Cells · 2020Article
- The Reducible Disulfide Proteome of Synaptosomes Supports a Role for Reversible Oxidations of Protein Thiols in the Maintenance of Neuronal Redox Homeostasis.Neurochemical research · 2020Article
- Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Large increases in cytosolic free Ca2+ ([Ca2+]i) activate several kinases that are important for neuronal plasticity, including Ca2+/calmodulin-dependent kinase II (CaMKII), protein kinase A (PKA), and protein kinase C (PKC). Because it is also known, mainly in non-neuronal systems, that superoxide radicals (O2-) activate these (and other) kinases and because O2- generation by mitochondria is in part [Ca2+]i dependent, we examined in hippocampal neurons the relationship between Ca2+ entry, O2- production, and kinase activity. We found that, after large stimulus-induced [Ca2+]i increases, O2- selectively produced by mitochondria near plasmalemmal sites of Ca2+ entry acts as a modulator to upregulate the two kinases, namely, CaMKII and PKA, whose activities are directly or indirectly phosphorylation dependent. The common mechanism involves O2- inhibition of inactivating protein phosphatases. Conversely, because small [Ca2+]i increases do not promote mitochondrial respiration and O2- generation, weak stimuli favor enhanced phosphatase activity, which therefore leads to suppressed kinase activity. Enhanced O2- production also promoted PKC activity but by a phosphatase-independent pathway. These results suggest that Ca2+-dependent upregulation of mitochondrial O2- production may be a general mechanism for linking Ca2+ entry to enhanced kinase activity and therefore to synaptic plasticity. This mechanism also represents yet another way that mitochondria, acting as calcium sensors, can play a role in neuronal signal transduction.
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