ArticleThe Journal of clinical investigation2014
Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04912609 (An Observational Study in Subjects With Spastic Paraplegia Type 11 Taking Trehalose), which is not on this map. Cited by 128 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
An Observational Study in Subjects With Spastic Paraplegia Type 11 Taking Trehalose
Who cites it
128 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Miglustat does not impact clinical progression in patients with spastic paraplegia type 11.Neurogenetics · 2025Trial
- Hereditary spastic paraplegia (HSP) gene 11 (Spg11) attenuates lipid accumulation in myeloid cells and neuroinflammation in the midbrain without affecting α-synuclein pathology.Journal of neuroinflammation · 2026Article
- Maspardin/SPG21 controls lysosome motility and TFEB phosphorylation through RAB7 positioning.The Journal of cell biology · 2026Article
- The Fragile Balance: Autophagy's Role in Neurodegenerative Disease Progression.Current neuropharmacology · 2026Review
- Small peptide P110 mitigates axonal degeneration of SPG15 patient iPSC-derived neurons by targeting mitochondrial dysfunction.Neurobiology of disease · 2025Article
- Endoplasmic reticulum junctions serve as a platform for endosome-lysosome interactions through their stop-and-go motion switching.Science advances · 2025Article
- Structural basis for membrane remodeling by the AP5-SPG11-SPG15 complex.Nature structural & molecular biology · 2025Article
- A depression-associated protein FKBP5 functions in autophagy initiation through scaffolding the VPS34 complex.Molecular neurobiology · 2025Article
- A competition network connects Rab5 and Rab11 GTPases at the surface of endocytic structures.iScience · 2025Article
- Bi-allelic variants in three genes encoding distinct subunits of the vesicular AP-5 complex cause hereditary macular dystrophy.American journal of human genetics · 2025Article
- Transcriptomic analysis reinforces the implication of spatacsin in neuroinflammation and neurodevelopment.Scientific reports · 2025Article
- Morphodynamical adaptation of the endolysosomal system to stress.The FEBS journal · 2025Review
- The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).Autophagy reports · 2025Review
- Axon demyelination and degeneration in a zebrafishOpen biology · 2024Article
- Downregulation of Protease Cathepsin D and Upregulation of Pathologic α-Synuclein Mediate Paucity of DNAJC6-Induced Degeneration of Dopaminergic Neurons.International journal of molecular sciences · 2024Article
- TRIM22 facilitates autophagosome-lysosome fusion by mediating the association of GABARAPs and PLEKHM1.Autophagy · 2024Article
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- Recent progresses in the late stages of autophagy.Cell insight · 2024Review
68 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
Autophagy allows cells to adapt to changes in their environment by coordinating the degradation and recycling of cellular components and organelles to maintain homeostasis. Lysosomes are organelles critical for terminating autophagy via their fusion with mature autophagosomes to generate autolysosomes that degrade autophagic materials; therefore, maintenance of the lysosomal population is essential for autophagy-dependent cellular clearance. Here, we have demonstrated that the two most common autosomal recessive hereditary spastic paraplegia gene products, the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR), a pathway that generates new lysosomes. Lysosomal targeting of spastizin required an intact FYVE domain, which binds phosphatidylinositol 3-phosphate. Loss of spastizin or spatacsin resulted in depletion of free lysosomes, which are competent to fuse with autophagosomes, and an accumulation of autolysosomes, reflecting a failure in ALR. Moreover, spastizin and spatacsin were essential components for the initiation of lysosomal tubulation. Together, these results link dysfunction of the autophagy/lysosomal biogenesis machinery to neurodegeneration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.