ArticleMolecular genetics and metabolism reports2014
Elevated Autophagy and Mitochondrial Dysfunction in the Smith-Lemli-Opitz Syndrome.
Article in Molecular genetics and metabolism reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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.
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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.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Compromised lipid metabolism, mitochondria respiration and neuroprotective effects in iPSC-derived astrocytes from a Smith-Lemli-Opitz syndrome patient.Human molecular genetics · 2025Article
- The Interplay of Oxidative Stress, Mitochondrial Dysfunction, and Neuroinflammation in Autism Spectrum Disorder: Behavioral Implications and Therapeutic Strategies.Brain sciences · 2025Review
- The multifaceted role of mitochondria in autism spectrum disorder.Molecular psychiatry · 2025Review
- Smith-Lemli-Opitz syndrome: A pathophysiological manifestation of the Bloch hypothesis.Frontiers in molecular biosciences · 2023Review
- Transcriptomic Changes Associated with Loss of Cell Viability Induced by Oxysterol Treatment of a Retinal Photoreceptor-Derived Cell Line: An In Vitro Model of Smith-Lemli-Opitz Syndrome.International journal of molecular sciences · 2021Article
- Desmosterolosis and desmosterol homeostasis in the developing mouse brain.Journal of inherited metabolic disease · 2019Article
- Is autophagy an elective strategy to protect neurons from dysregulated cholesterol metabolism?Neural regeneration research · 2019Review
- Neuronal Dysfunction Associated with Cholesterol Deregulation.International journal of molecular sciences · 2018Article
- Mitochondrial dysfunction and autism: comprehensive genetic analyses of children with autism and mtDNA deletion.Behavioral and brain functions : BBF · 2018Article
- Compromised phagosome maturation underlies RPE pathology in cell culture and whole animal models of Smith-Lemli-Opitz Syndrome.Autophagy · 2018Article
- Glycine Protects H9C2 Cardiomyocytes from High Glucose- and Hypoxia/Reoxygenation-Induced Injury via Inhibiting PKCJournal of diabetes research · 2018Article
- Probes for protein adduction in cholesterol biosynthesis disorders: Alkynyl lanosterol as a viable sterol precursor.Redox biology · 2017Article
- Differential cytotoxic effects of 7-dehydrocholesterol-derived oxysterols on cultured retina-derived cells: Dependence on sterol structure, cell type, and density.Experimental eye research · 2016Article
- miR-101 reverses hypomethylation of the PRDM16 promoter to disrupt mitochondrial function in astrocytoma cells.Oncotarget · 2016Article
- Innovative Target Therapies Are Able to Block the Inflammation Associated with Dysfunction of the Cholesterol Biosynthesis Pathway.International journal of molecular sciences · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 7 institutions in 1 country.
Funding
Abstract
Smith-Lemli-Opitz syndrome (SLOS) is a congenital, autosomal recessive metabolic and developmental disorder caused by mutations in the enzyme which catalyzes the reduction of 7-dehydrocholesterol (7DHC) to cholesterol. Herein we show that dermal fibroblasts obtained from SLOS children display increased basal levels of LC3B-II, the hallmark protein signifying increased autophagy. The elevated LC3B-II is accompanied by increased beclin-1 and cellular autophagosome content. We also show that the LC3B-II concentration in SLOS cells is directly proportional to the cellular concentration of 7DHC, suggesting that the increased autophagy is caused by 7DHC accumulation secondary to defective DHCR7. Further, the increased basal LC3B-II levels were decreased significantly by pretreating the cells with antioxidants implicating a role for oxidative stress in elevating autophagy in SLOS cells. Considering the possible source of oxidative stress, we examined mitochondrial function in the SLOS cells using JC-1 assay and found significant mitochondrial dysfunction compared to mitochondria in control cells. In addition, the levels of PINK1 which targets dysfunctional mitochondria for removal by the autophagic pathway are elevated in SLOS cells, consistent with mitochondrial dysfunction as a stimulant of mitophagy in SLOS. This suggests the increase in autophagic activity may be protective, i.e., to remove dysfunctional mitochondria. Taken together, these studies are consistent with a role for mitochondrial dysfunction leading to increased autophagy in SLOS pathophysiology.
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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.