The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
The inhibition of TDP-43 mitochondrial localization blocks its neuronal toxicity
Open accessAbstract
Genetic mutations in TAR DNA-binding protein 43 (TARDBP, also known as TDP-43) cause amyotrophic lateral sclerosis (ALS), and an increase in the presence of TDP-43 (encoded by TARDBP) in the cytoplasm is a prominent histopathological feature of degenerating neurons in various neurodegenerative diseases. However, the molecular mechanisms by which TDP-43 contributes to ALS pathophysiology remain elusive. Here we have found that TDP-43 accumulates in the mitochondria of neurons in subjects with ALS or frontotemporal dementia (FTD). Disease-associated mutations increase TDP-43 mitochondrial localization. In mitochondria, wild-type (WT) and mutant TDP-43 preferentially bind mitochondria-transcribed messenger RNAs (mRNAs) encoding respiratory complex I subunits ND3 and ND6, impair their expression and specifically cause complex I disassembly. The suppression of TDP-43 mitochondrial localization abolishes WT and mutant TDP-43-induced mitochondrial dysfunction and neuronal loss, and improves phenotypes of transgenic mutant TDP-43 mice. Thus, our studies link TDP-43 toxicity directly to mitochondrial bioenergetics and propose the targeting of TDP-43 mitochondrial localization as a promising therapeutic approach for neurodegeneration.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
Locating proteins in the cell using TargetP, SignalP and related tools
Emanuelsson, O., Brunak, S., von Heijne, G., & Nielsen, H. (2007) · Nature Protocols · doi:10.1038/nprot.2007.131 · Cited by 3,188
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
THE MITOCHONDRIAL DEATH/LIFE REGULATOR IN APOPTOSIS AND NECROSIS
Kroemer, G., Dallaporta, B., & Resche-Rigon, M. (1998) · Annual Review of Physiology · doi:10.1146/annurev.physiol.60.1.619 · Cited by 1,963
Kaech, S., & Banker, G. (2006) · Nature Protocols · doi:10.1038/nprot.2006.356 · Cited by 1,659
Computational Method to Predict Mitochondrially Imported Proteins and their Targeting Sequences
Claros, M. G., & Vincens, P. (1996) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1996.00779.x · Cited by 1,643
TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis
Kabashi, E., Valdmanis, P. N., Dion, P., Spiegelman, D., McConkey, B. J., Velde, C. V., Bouchard, J.-P., Lacomblez, L., Pochigaeva, K., Salachas, F., et al. (2008) · Nature Genetics · doi:10.1038/ng.132 · Cited by 1,544
Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43
Polymenidou, M., Lagier-Tourenne, C., Hutt, K. R., Huelga, S. C., Moran, J., Liang, T. Y., Ling, S.-C., Sun, E., Wancewicz, E., Mazur, C., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2779 · Cited by 1,335
Cogliati, S., Frezza, C., Soriano, M. E., Varanita, T., Quintana-Cabrera, R., Corrado, M., Cipolat, S., Costa, V., Casarin, A., Gomes, L. C., et al. (2013) · Cell · doi:10.1016/j.cell.2013.08.032 · Cited by 1,265
Impaired Balance of Mitochondrial Fission and Fusion in Alzheimer's Disease
Wang, X., Su, B., Lee, H.-G., Li, X., Perry, G., Smith, M. A., & Zhu, X. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.1357-09.2009 · Cited by 1,224
Self-citation
Cited by
TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS
Yu, C.-H., Davidson, S., Harapas, C. R., Hilton, J. B., Mlodzianoski, M. J., Laohamonthonkul, P., Louis, C., Low, R. R. J., Moecking, J., De Nardo, D., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.020 · Cited by 1,019
Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis
Prasad, A., Bharathi, V., Sivalingam, V., Girdhar, A., & Patel, B. K. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00025 · Cited by 774
Neuronal Cell Death Mechanisms in Major Neurodegenerative Diseases
Chi, H., Chang, H.-Y., & Sang, T.-K. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103082 · Cited by 412
Mitra, J., Guerrero, E. N., Hegde, P. M., Liachko, N. F., Wang, H., Vasquez, V., Gao, J., Pandey, A., Taylor, J. P., Kraemer, B. C., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1818415116 · Cited by 305
Oxidative stress and mitochondrial impairment: Key drivers in neurodegenerative disorders
Wen, P., Sun, Z., Gou, F., Wang, J., Fan, Q., Zhao, D., & Yang, L. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102667 · Cited by 253
Metadata
- Authors
- Wang, W., Wang, L., Lu, J., Siedlak, S. L., Fujioka, H., Liang, J., Jiang, S., Ma, X., Jiang, Z., da Rocha, E. L., Sheng, M., Choi, H., Lerou, P. H., Li, H., & Wang, X.
- Venue
- Nature Medicine
- Published
- 2016-06-27
- Volume
- 22
- Issue
- 8
- Pages
- 869-878
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2472573833
- Cited by
- 459
- References
- 63
- FWCI
- 22.96
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: The inhibition of TDP-43 mitochondrial localization blocks its neuronal toxicity. https://app.cochat.ai/papers/10.1038/nm.4130
- The paper
- Wang, W., Wang, L., Lu, J., Siedlak, S. L., Fujioka, H., Liang, J., Jiang, S., Ma, X., Jiang, Z., da Rocha, E. L., Sheng, M., Choi, H., Lerou, P. H., Li, H., & Wang, X. (2016). The inhibition of TDP-43 mitochondrial localization blocks its neuronal toxicity. Nature Medicine. https://doi.org/10.1038/nm.4130
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
