The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
ALS / FTD ‐associated FUS activates GSK ‐3β to disrupt the VAPB – PTPIP 51 interaction and ER –mitochondria associations
Open accessAbstract
Defective FUS metabolism is strongly associated with amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD), but the mechanisms linking FUS to disease are not properly understood. However, many of the functions disrupted in ALS/FTD are regulated by signalling between the endoplasmic reticulum (ER) and mitochondria. This signalling is facilitated by close physical associations between the two organelles that are mediated by binding of the integral ER protein VAPB to the outer mitochondrial membrane protein PTPIP51, which act as molecular scaffolds to tether the two organelles. Here, we show that FUS disrupts the VAPB-PTPIP51 interaction and ER-mitochondria associations. These disruptions are accompanied by perturbation of Ca(2+) uptake by mitochondria following its release from ER stores, which is a physiological read-out of ER-mitochondria contacts. We also demonstrate that mitochondrial ATP production is impaired in FUS-expressing cells; mitochondrial ATP production is linked to Ca(2+) levels. Finally, we demonstrate that the FUS-induced reductions to ER-mitochondria associations and are linked to activation of glycogen synthase kinase-3β (GSK-3β), a kinase already strongly associated with ALS/FTD.
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Cites
Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., Bruce, J., Schuck, T., Grossman, M., Clark, C. M., et al. (2006) · Science · doi:10.1126/science.1134108 · Cited by 6,576
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TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis
Sreedharan, J., Blair, I. P., Tripathi, V. B., Hu, X., Vance, C., Rogelj, B., Ackerley, S., Durnall, J. C., Williams, K. L., Buratti, E., et al. (2008) · Science · doi:10.1126/science.1154584 · Cited by 2,630
Self-citationMitofusin 2 tethers endoplasmic reticulum to mitochondria
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Direct observation of individual endogenous protein complexes in situ by proximity ligation
Söderberg, O., Gullberg, M., Jarvius, M., Ridderstråle, K., Leuchowius, K.-J., Jarvius, J., Wester, K., Hydbring, P., Bahram, F., Larsson, L.-G., et al. (2006) · Nature Methods · doi:10.1038/nmeth947 · Cited by 2,419
Converging Mechanisms in ALS and FTD: Disrupted RNA and Protein Homeostasis
Ling, S.-C., Polymenidou, M., & Cleveland, D. W. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.033 · Cited by 1,811 · cited 2×
“ALS is the most common form of motor neuron disease, and FTD is the second most common form of presenile dementia after Alzheimer’s disease [7].”
Endoplasmic reticulum-mitochondria contacts: Function of the junction
Rowland, A. A., & Voeltz, G. K. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3440 · Cited by 1,018 · cited 1×
“ER–mitochondria associations control Ca exchange between the two organelles, and this can impact upon the ability of mitochondria to generate ATP [1,45].”
Wong, Y. C., & Holzbaur, E. L. F. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1405752111 · Cited by 812
Upregulated function of mitochondria‐associated ER membranes in Alzheimer disease
Area‐Gomez, E., del Carmen Lara Castillo, M., Tambini, M. D., Guardia‐Laguarta, C., de Groof, A. J. C., Madra, M., Ikenouchi, J., Umeda, M., Bird, T. D., Sturley, S. L., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.202 · Cited by 638
Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis
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Hajam, Y. A., Rani, R., Ganie, S. Y., Sheikh, T. A., Javaid, D., Qadri, S. S., Pramodh, S., Alsulimani, A., Alkhanani, M. F., Harakeh, S., et al. (2022) · Cells · doi:10.3390/cells11030552 · Cited by 915
Endoplasmic reticulum-mitochondrial contactology: structure and signaling functions
Csordás, G., Weaver, D., & Hajnóczky, G. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.02.009 · Cited by 625
The role of mitochondria in amyotrophic lateral sclerosis
Smith, E. F., Shaw, P. J., & De Vos, K. J. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2017.06.052 · Cited by 559
Self-citationCalcium, mitochondria and cell metabolism: A functional triangle in bioenergetics
Rossi, A., Pizzo, P., & Filadi, R. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2018.10.016 · Cited by 489
HDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients
Guo, W., Naujock, M., Fumagalli, L., Vandoorne, T., Baatsen, P., Boon, R., Ordovás, L., Patel, A., Welters, M., Vanwelden, T., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00911-y · Cited by 373
Metadata
- Authors
- Stoica, R., Paillusson, S., Gomez‐Suaga, P., Mitchell, J. C., Lau, D. H., Gray, E. H., Sancho, R. M., Vizcay‐Barrena, G., De Vos, K. J., Shaw, C. E., Hanger, D. P., Noble, W., & Miller, C. C.
- Venue
- EMBO reports
- Published
- 2016-07-14
- Volume
- 17
- Issue
- 9
- Pages
- 1326-1342
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- OpenAlex
- W2473774898
- Cited by
- 252
- References
- 13
- FWCI
- 15.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Stoica, R., Paillusson, S., Gomez‐Suaga, P., Mitchell, J. C., Lau, D. H., Gray, E. H., Sancho, R. M., Vizcay‐Barrena, G., De Vos, K. J., Shaw, C. E., Hanger, D. P., Noble, W., & Miller, C. C. (2016). ALS / FTD ‐associated FUS activates GSK ‐3β to disrupt the VAPB – PTPIP 51 interaction and ER –mitochondria associations. EMBO reports. https://doi.org/10.15252/embr.201541726
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