Autosomal recessive cutis laxa type 3A is caused by mutations in ALDH18A1, a gene encoding the mitochondrial enzyme Δ(1)-pyrroline-5-carboxylate synthase (P5CS). It is a rare disorder with only six pathogenic mutations and 10 affected individuals from five families previously described in the literature. Here we report the identification of novel compound heterozygous missense mutations in two affected siblings from a Lebanese family by whole-exome sequencing. The mutations alter a conserved C-terminal domain of the encoded protein and reduce protein stability as determined through Western blot analysis of patient fibroblasts. Patient fibroblasts exhibit a lipid droplet phenotype similar to that recently reported in Warburg Micro syndrome, a disorder with similar features but hitherto unrelated cellular etiology.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113272PMC
http://dx.doi.org/10.1002/mgg3.70DOI Listing

Publication Analysis

Top Keywords

lipid droplet
8
droplet phenotype
8
autosomal recessive
8
recessive cutis
8
cutis laxa
8
laxa type
8
warburg micro
8
micro syndrome
8
patient fibroblasts
8
loss aldh18a1
4

Similar Publications

Background: Endocrine-disrupting chemicals (EDCs) interfere with the endocrine system and negatively impact reproductive health. Biochanin A (BCA), an isoflavone with anti-inflammatory and estrogen-like properties, has been identified as one such EDC. This study investigates the effects of BCA on transcription, metabolism, and hormone regulation in primary human granulosa cells (GCs), with a specific focus on the activation of bitter taste receptors (TAS2Rs).

View Article and Find Full Text PDF

Mitochondria derive the majority of their lipids from other organelles through contact sites. These lipids, primarily phosphoglycerolipids, are the main components of mitochondrial membranes. In the cell, neutral lipids like triacylglycerides (TAGs) are stored in lipid droplets, playing an important role in maintaining cellular health.

View Article and Find Full Text PDF

Timosaponin B II as a novel KEAP1-NRF2 inhibitor to alleviate alcoholic liver disease:Receptor structure-based virtual screening and biological evaluation.

Chem Biol Interact

January 2025

Anhui Prevention and Control Engineering Research Center for Fatty Liver Disease, Hefei, Anhui, 230032,P. R. China; The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Hefei, China; Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, China. Electronic address:

Oxidative stress induced by excess ethanol is an important factor in the progression of alcoholic liver disease (ALD). In recent years, inhibiting Kelch-like ECH-associated protein 1 (KEAP1) to activate the antioxidant regulator Nuclear factor erythroid 2-related factor 2 (NRF2) has been considered an effective strategy for treating oxidative stress-related diseases, but its application in ALD remains insufficiently explored. This study aims to discover high-affinity inhibitors targeting the KEAP1 receptor.

View Article and Find Full Text PDF

Mycoplasma pneumoniae drives macrophage lipid uptake via GlpD-mediated oxidation, facilitating foam cell formation.

Int J Med Microbiol

January 2025

Division of Microbiology, Department of Infectious Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.

Cardiovascular diseases, primarily caused by atherosclerosis, are a major public health concern worldwide. Atherosclerosis is characterized by chronic inflammation and lipid accumulation in the arterial wall, leading to plaque formation. In this process, macrophages play a crucial role by ingesting lipids and transforming into foam cells, which contribute to plaque instability and cardiovascular events.

View Article and Find Full Text PDF

You better keep an eye on your contacts.

Cell Calcium

January 2025

Section on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.

Membrane contact sites (MCS) are specialized compartments found in all eukaryotic cells that are formed between membranes of different organelles that are in close proximity. MCS have important functions as they are sites of efficient transfer of molecules between neighboring organelles. Two recent articles have used the splitFAST system to mark and follow the dynamics of membrane contact sites and used the method to highlight the importance of MCS between the endoplasmic reticulum (ER) and lipid droplets in metabolic adaptation and MCS between the ER and mitochondria in Ca signal propagation.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!