The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
PKA Phosphorylation of NCLX Reverses Mitochondrial Calcium Overload and Depolarization, Promoting Survival of PINK1-Deficient Dopaminergic Neurons
Open accessAbstract
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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Cites
Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1
Valente, E. M., Abou-Sleiman, P. M., Caputo, V., Muqit, M. M. K., Harvey, K., Gispert, S., Ali, Z., Del Turco, D., Bentivoglio, A. R., Healy, D. G., et al. (2004) · Science · doi:10.1126/science.1096284 · Cited by 3,481
The mitochondrial permeability transition pore and its role in cell death
CROMPTON, M. (1999) · Biochemical Journal · doi:10.1042/bj3410233 · Cited by 2,432
Soluble Adenylyl Cyclase as an Evolutionarily Conserved Bicarbonate Sensor
Chen, Y., Cann, M. J., Litvin, T. N., Iourgenko, V., Sinclair, M. L., Levin, L. R., & Buck, J. (2000) · Science · doi:10.1126/science.289.5479.625 · Cited by 846
Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress
Gautier, C. A., Kitada, T., & Shen, J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802076105 · Cited by 698
Gandhi, S., Wood-Kaczmar, A., Yao, Z., Plun-Favreau, H., Deas, E., Klupsch, K., Downward, J., Latchman, D. S., Tabrizi, S. J., Wood, N. W., et al. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.02.013 · Cited by 682
Self-citationPINK1 is necessary for long term survival and mitochondrial function in human dopaminergic neurons
Wood-Kaczmar, A., Gandhi, S., Yao, Z., Abramov, A. S. Y., Miljan, E. A., Keen, G., Stanyer, L., Hargreaves, I., Klupsch, K., Deas, E., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002455 · Cited by 316
Self-citationDepletion of PINK1 affects mitochondrial metabolism, calcium homeostasis and energy maintenance
Heeman, B., Van den Haute, C., Aelvoet, S.-A., Valsecchi, F., Rodenburg, R. J., Reumers, V., Debyser, Z., Callewaert, G., Koopman, W. J. H., Willems, P. H. G. M., et al. (2011) · Journal of Cell Science · doi:10.1242/jcs.078303 · Cited by 198
Cited by
The machineries, regulation and cellular functions of mitochondrial calcium
Giorgi, C., Marchi, S., & Pinton, P. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0052-8 · Cited by 941
Role of mitochondrial ROS in the brain: from physiology to neurodegeneration
Angelova, P. R., & Abramov, A. Y. (2018) · FEBS Letters · doi:10.1002/1873-3468.12964 · Cited by 789
Self-citationPark, J.-S., Davis, R. L., & Sue, C. M. (2018) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-018-0829-3 · Cited by 516
Oxidative Stress in Neurodegenerative Diseases: From a Mitochondrial Point of View
Cenini, G., Lloret, A., & Cascella, R. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/2105607 · Cited by 499
Excitotoxicity, calcium and mitochondria: a triad in synaptic neurodegeneration
Verma, M., Lizama, B. N., & Chu, C. T. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-021-00278-7 · Cited by 451
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Metadata
- Authors
- Kostic, M., Ludtmann, M. H. R., Bading, H., Hershfinkel, M., Steer, E., Chu, C. T., Abramov, A. Y., & Sekler, I.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 13
- Issue
- 2
- Pages
- 376-386
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2165811472
- Cited by
- 177
- References
- 7
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- gold
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- Kostic, M., Ludtmann, M. H. R., Bading, H., Hershfinkel, M., Steer, E., Chu, C. T., Abramov, A. Y., & Sekler, I. (2015). PKA Phosphorylation of NCLX Reverses Mitochondrial Calcium Overload and Depolarization, Promoting Survival of PINK1-Deficient Dopaminergic Neurons. Cell Reports. https://doi.org/10.1016/j.celrep.2015.08.079
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