AI Article Synopsis
- Sphingolipids are essential for membrane structure and cellular signaling, with ceramide being a key molecule in this process generated by specific enzymes called ceramide synthases (CerS).
- The small heat shock protein 27 (Hsp27) specifically interacts with and inhibits CerS1, affecting ceramide production; this interaction is crucial for understanding CerS regulation.
- Hsp27's activity influences mitochondrial function and mitophagy, highlighting its role in the cellular response to stress and its significance in managing CerS1-related processes.
Article Abstract
Sphingolipids have key functions in membrane structure and cellular signaling. Ceramide is the central molecule of the sphingolipid metabolism and is generated by ceramide synthases (CerS) in the de novo pathway. Despite their critical function, mechanisms regulating CerS remain largely unknown. Using an unbiased proteomics approach, we find that the small heat shock protein 27 (Hsp27) interacts specifically with CerS1 but not other CerS. Functionally, our data show that Hsp27 acts as an endogenous inhibitor of CerS1. Wild-type Hsp27, but not a mutant deficient in CerS1 binding, inhibits CerS1 activity. Additionally, silencing of Hsp27 enhances CerS1-generated ceramide accumulation in cells. Moreover, phosphorylation of Hsp27 modulates Hsp27-CerS1 interaction and CerS1 activity in acute stress-response conditions. Biologically, we show that Hsp27 knockdown impedes mitochondrial function and induces lethal mitophagy in a CerS1-dependent manner. Overall, we identify an important mode of CerS1 regulation and CerS1-mediated mitophagy through protein-protein interaction with Hsp27.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10591768 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2023.113081 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Wu-Mei-Wan enhances brown adipose tissue function and white adipose browning in obese mice via upregulation of HSF1.
Chin Med
January 2025
Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
Background: This research aims to explore the anti-obesity potential of Wu-Mei-Wan (WMW), particularly its effects on adipose tissue regulation in obese mice induced by a high-fat diet (HFD). The study focuses on understanding the role of heat shock factor 1 (HSF1) in mediating these effects.
Methods: HFD-induced obese mice were treated with WMW.
Assessing the efficacy of synthetic compounds foliar sprays in alleviating terminal heat stress in late-sown wheat ().
Funct Plant Biol
January 2025
Krishi Vigyan Kendra, Siwan, Dr. RPCAU, Pusa, Bihar, India.
Detrimental effects of terminal heat stress could be mitigated by exogenous application of synthetic compounds by preserving cell membrane integrity and protecting against oxidative damage. A field experiment was conducted to test the application of seven synthetic compounds on wheat growth traits: (1) thiourea (20 mM and 40mM); (2) potassium nitrate (1% and 2%); (3) sodium nitroprusside (400 μg mL-1 and 800μg mL-1 ); (4) dithiothreitol (25 ppm and 50ppm); (5) salicylic acid (100 ppm and 200ppm); (6) thioglycolic acid (200 ppm and 500ppm); and (7) putrescine (4 mM and 6mM). These compounds were applied at the anthesis and grain-filling stages to enhance physio-biochemical traits and yield attributes of wheat (Triticum aestivum ) cvs GW-11 and GW-496 under terminal heat stress.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Delaware State University, Dover, DE, USA.
Background: Aggregation of transactive response DNA binding protein 43 (TDP-43) is the major pathological feature of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recently, in up to 50% of Alzheimer's disease (AD) cases TDP-43 pathology was discovered and this pathology has been referred to as limbic-predominant age-related TDP43 encephalopathy (LATE). Several studies reported that TDP-43 binds to heat shock protein family B (small) member 1 (HSPB1 or HSP27) but no functional evaluation of this interaction has been explored.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Ohio State University College of Medicine, Neurobiology of Aging & Resilience Center, Columbus, OH, USA.
Background: The cerebrovasculature is an essential component of brain homeostasis. Cerebrovascular disorders are associated with an increased risk for neurodegenerative diseases, including Alzheimer's disease (AD). However, the mechanisms by which cerebrovascular dysfunction contributes to neurodegeneration are poorly understood.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Rush University Medical Center, Chicago, IL, USA.
Background: Abnormal brain insulin signaling has been associated with Alzheimer's disease pathology and a faster rate of late-life cognitive decline. However, the underlying mechanisms remain unclear. In this study, we examined whether AD-related cortical proteins identified using targeted-proteomics play a role in the association of brain insulin signaling and cognitive decline.
View Article and Find Full Text PDFWant 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!