The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
Motor neuron mitochondrial dysfunction in spinal muscular atrophy
Open accessAbstract
Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, predominantly affects high metabolic tissues including motor neurons, skeletal muscles and the heart. Although the genetic cause of SMA has been identified, mechanisms underlying tissue-specific vulnerability are not well understood. To study these mechanisms, we carried out a deep sequencing analysis of the transcriptome of spinal motor neurons in an SMA mouse model, in which we unexpectedly found changes in many genes associated with mitochondrial bioenergetics. Importantly, functional measurement of mitochondrial activities showed decreased basal and maximal mitochondrial respiration in motor neurons from SMA mice. Using a reduction-oxidation sensitive GFP and fluorescence sensors specifically targeted to mitochondria, we found increased oxidative stress level and impaired mitochondrial membrane potential in motor neurons affected by SMA. In addition, mitochondrial mobility was impaired in SMA disease conditions, with decreased retrograde transport but no effect on anterograde transport. We also found significantly increased fragmentation of the mitochondrial network in primary motor neurons from SMA mice, with no change in mitochondria density. Electron microscopy study of SMA mouse spinal cord revealed mitochondria fragmentation, edema and concentric lamellar inclusions in motor neurons affected by the disease. Intriguingly, these functional and structural deficiencies in the SMA mouse model occur during the presymptomatic stage of disease, suggesting a role in initiating SMA. Altogether, our findings reveal a critical role for mitochondrial defects in SMA pathogenesis and suggest a novel target for improving tissue health in the disease.
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.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Analysis of peripheral blood monocyte transcriptomes from HD patients has revealed a proinflammatory phenotype, perhaps reflecting a priming effect of mutant HTT (165).”
From Microglia Function in the Central Nervous System During Health and Neurodegeneration (2017) · cites this paper as [165]
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
Mitochondrial Dysfunction and Oxidative Stress in Neurodegenerative Diseases
Lin, M. T., & Beal, M. F. (2006) · Nature · doi:10.1038/nature05292 · Cited by 6,455
Identification and characterization of a spinal muscular atrophy-determining gene
Lefebvre, S., Bürglen, L., Reboullet, S., Clermont, O., Burlet, P., Viollet, L., Bénichou, B., Cruaud, C., Millasseau, P., Zeviani, M., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90460-3 · Cited by 3,995
Directed differentiation of embryonic stem cells into motor neurons.
Wichterle, H., Lieberam, I., Porter, J. A., & Jessell, T. (2002) · Cell · doi:10.1016/s0092-8674(02)00835-8 · Cited by 1,792
During autophagy mitochondria elongate, are spared from degradation and sustain cell viability
Gomes, L. C., Benedetto, G. D., & Scorrano, L. (2011) · Nature Cell Biology · doi:10.1038/ncb2220 · Cited by 1,735
Mitochondrial Respiratory-Chain Diseases
DiMauro, S., & Schon, E. A. (2003) · New England Journal of Medicine · doi:10.1056/nejmra022567 · Cited by 1,672
Disruption of Fusion Results in Mitochondrial Heterogeneity and Dysfunction
Chen, H., Chomyn, A., & Chan, D. C. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503062200 · Cited by 1,376 · cited 2×
“Increased mitochondrial fusion protects against neurodegeneration (48), while disruption of fusion leads to smaller, fragmented mitochondria that display reduced membrane potential and impaired respiration (35,49).”
BackgroundCogliati, 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
Mitochondrial dynamics and inheritance during cell division, development and disease
Mishra, P., & Chan, D. C. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3877 · Cited by 1,076
Lunn, M. R., & Wang, C. H. (2008) · The Lancet · doi:10.1016/s0140-6736(08)60921-6 · Cited by 1,010
Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration
Sheng, Z., & Cai, Q. (2012) · Nature reviews. Neuroscience · doi:10.1038/nrn3156 · Cited by 940
Cited by
Sorted by citations
Items 101–119 of 119
Deguise, M., Pileggi, C. A., Beauvais, A., Tierney, A., Chehadé, L., Repentigny, Y. D., Michaud, J., Hurtado, M. L., Lamont, D. J., Atrih, A., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.29.051938 · Cited by 3
Using Genomic Data to Find Disease-Modifying Loci in Huntington’s Disease (HD)
Holmans, P., & Stone, T. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7825-0_20 · Cited by 2
SMN promotes mitochondrial metabolic maturation during myogenesis by regulating the MYOD-miRNA axisPreprint
Ikenaka, A., Kitagawa, Y., Yoshida, M., Lin, C., Niwa, A., Nakahata, T., & Saito, M. K. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.02.13.480288 · Cited by 2
Thelen, M. P., Wirth, B., & Kye, M. J. (2020) · Research Square · doi:10.21203/rs.3.rs-49251/v1 · Cited by 2
Advances in the Potential Role and Mechanism of Fibroblasts in Spinal Muscular Atrophy
Chen, C., Zhang, J., Xue, C., Liu, D., & Li, S. (2025) · Cell Biochemistry and Function · doi:10.1002/cbf.70118 · Cited by 1
Brokate-Llanos, A. M., Beltran, M., Garzón, A., Garcerá, A., Miralles, M. P., Nos, F. C., Campoy-López, A., Soler, R. M., Muñoz, M. J., & Pérez‐Pulido, A. J. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118610 · Cited by 1
When barriers fail: the role of endothelial dysfunction in rare pediatric neuromuscular diseases
Agafonova, A., Cosentino, A., Prinzi, C., Parano, C., Salinaro, A. T., Scuto, M. C., Riccioli, G., Lupo, G., & Anfuso, C. D. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1834381 · Cited by 1
Imaging mitochondria live or fixed muscle tissues
Bader, C. A., Bader, C. A., Sorvina, A., Darby, J. R. T., Lock, M. C., Soo, J. Y., Johnson, I. R., Caporale, C., Massi, M., Stagni, S., et al. (2018) · Protocol Exchange · doi:10.1038/protex.2018.101 · Cited by 1
Habets, L. E., Bartels, B., Asselman, F., Hulzebos, E. H. J., Stegeman, D. F., Jeneson, J. A. L., & van der Pol, W. L. (2022) · Journal of Neuromuscular Diseases · doi:10.3233/jnd-210765 · Cited by 1
Nichterwitz, S., Storvall, H., Nijssen, J., Comley, L. H., Allodi, I., van der Lee, M., Schweingruber, C., Deng, Q., Sandberg, R., & Hedlund, E. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/356113 · Cited by 1
Grandi, F., Astord, S., Pezet, S., Gidaja, E., Mazzucchi, S., Chapart, M., Vasseur, S., Mamchaoui, K., & Smeriglio, P. (2024) · bioRxiv · doi:10.1101/2024.02.29.582680 · Cited by 1
Rosignol, I., Dokuzluoglu, Z., Caldarelli, A., Oprişoreanu, A., Ushakova, S., Siddiqui, T., Grover, R., Guerlich, H., Falkenburger, B. H., Diez, S., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.07.663525 · Cited by 1
Fatigability in spinal muscular atrophy
Bartels, B. (2021) · doi:10.33540/181
Thelen, M. P., Wirth, B., & Kye, M. J. (2020) · Figshare · doi:10.6084/m9.figshare.13481043
Thelen, M. P., Wirth, B., & Kye, M. J. (2020) · Figshare · doi:10.6084/m9.figshare.13481037
Nusinersen rescues taurine deficiency in patients with type 1 Spinal Muscular Atrophy
di Vito, R., Hassan, A., Nuzzo, T., Caretto, A., Panicucci, C., Bruno, C., Bertini, E., D’Amico, A., Vercelli, A., Boido, M., et al. (2026) · Communications Medicine · doi:10.1038/s43856-026-01434-8
D'amico, D. (2020) · theses.fr (ABES) · doi:10.70675/6e54c5b3zdabfz4677z9604zfcce72b7ed92
Spinal muscular atrophy: Biology, pathogenesis, and therapeutic advances
René, C. A., & Parks, R. J. (2026) · Therapeutic Advances in Neurological Disorders · doi:10.1177/17562864261480901
Metadata
- Authors
- Miller, N., Shi, H., Zelikovich, A. S., & Ma, Y.-C.
- Affiliations
- Northwestern University (US)
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-08-03
- Volume
- 25
- Issue
- 16
- Pages
- 3395-3406
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC5179954
- OpenAlex
- W2504137115
- Cited by
- 119
- References
- 65
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 11 · 2023: 13 · 2022: 12 · 2021: 18 · 2020: 19 · 2019: 5 · 2018: 17 · 2017: 11 · 2016: 1
- FWCI
- 8.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Hartwell Foundation
- Cure SMA
- Feinberg Foundation
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS094564)
- Topics
- Health Sciences › Medicine › Genetics (clinical) › Neurogenetic and Muscular Disorders Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- spinal muscular atrophy, motor neurons, mitochondrial dysfunction, mitochondrial respiration, oxidative stress, mitochondrial membrane potential, mitochondrial transport, mitochondrial fragmentation, presymptomatic disease, SMA mouse model, mitochondrial bioenergetics
- MeSH terms
- Animals, Disease Models, Animal, Humans, Microscopy, Electron, Mitochondria, Motor Neurons, Muscular Atrophy, Spinal, Myocardium, Spinal Cord, Oxidative Stress, Muscle, Skeletal, Mice, Membrane Potential, Mitochondrial, High-Throughput Nucleotide Sequencing, Transcriptome
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
