AI Article Synopsis
- Autophagy is usually triggered by stress like starvation or mitochondrial damage, but some cells activate it through unclear ways.
- Researchers found that the protein C15ORF48 is crucial for activating this stress-independent autophagy, which helps maintain cell survival and reduces oxidative stress.
- Mice lacking C15orf48 show decreased autophagy in specific cells and develop autoimmune issues, highlighting the importance of C15ORF48 in regulating self-tolerance in the immune system.
Article Abstract
Autophagy is primarily activated by cellular stress, such as starvation or mitochondrial damage. However, stress-independent autophagy is activated by unclear mechanisms in several cell types, such as thymic epithelial cells (TECs). Here we report that the mitochondrial protein, C15ORF48, is a critical inducer of stress-independent autophagy. Mechanistically, C15ORF48 reduces the mitochondrial membrane potential and lowers intracellular ATP levels, thereby activating AMP-activated protein kinase and its downstream Unc-51-like kinase 1. Interestingly, C15ORF48-dependent induction of autophagy upregulates intracellular glutathione levels, promoting cell survival by reducing oxidative stress. Mice deficient in C15orf48 show a reduction in stress-independent autophagy in TECs, but not in typical starvation-induced autophagy in skeletal muscles. Moreover, C15orf48 mice develop autoimmunity, which is consistent with the fact that the stress-independent autophagy in TECs is crucial for the thymic self-tolerance. These results suggest that C15ORF48 induces stress-independent autophagy, thereby regulating oxidative stress and self-tolerance.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10831050 | PMC |
| http://dx.doi.org/10.1038/s41467-024-45206-1 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cisplatin Nephrotoxicity Is Critically Mediated by the Availability of BECLIN1.
Int J Mol Sci
February 2024
III Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Cisplatin nephrotoxicity is a critical limitation of solid cancer treatment. Until now, the complex interplay of various pathophysiological mechanisms leading to proximal tubular cell apoptosis after cisplatin exposure has not been fully understood. In our study, we assessed the role of the autophagy-related protein BECLIN1 (ATG6) in cisplatin-induced acute renal injury (AKI)-a candidate protein involved in autophagy and with putative impact on apoptosis by harboring a B-cell lymphoma 2 (BCL2) interaction site of unknown significance.
View Article and Find Full Text PDFMitochondrial protein C15ORF48 is a stress-independent inducer of autophagy that regulates oxidative stress and autoimmunity.
Nat Commun
February 2024
Department of Molecular Cardiovascular Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675, Japan.
Article Synopsis
- Autophagy is usually triggered by stress like starvation or mitochondrial damage, but some cells activate it through unclear ways.
- Researchers found that the protein C15ORF48 is crucial for activating this stress-independent autophagy, which helps maintain cell survival and reduces oxidative stress.
- Mice lacking C15orf48 show decreased autophagy in specific cells and develop autoimmune issues, highlighting the importance of C15ORF48 in regulating self-tolerance in the immune system.
F-box protein FBXO41 suppresses breast cancer growth by inducing autophagic cell death through facilitating proteasomal degradation of oncogene SKP2.
Int J Biochem Cell Biol
June 2022
Molecular Oncology Laboratory, National Centre for Cell Science, Ganeshkhind Road, Pune, Maharashtra 411007, India. Electronic address:
F-box proteins form SCF (Cullin1, SKP1 and F-box-protein) ubiquitin ligase complexes to ubiquitinate cellular proteins. They play key role in several biological processes, including cell cycle progression, cellular signaling, stress response and cell death pathways. Therefore, deregulation of F-box proteins is closely associated with cancer progression.
View Article and Find Full Text PDFAmbient particulate matter triggers defective autophagy and hijacks endothelial cell renewal through oxidative stress-independent lysosomal impairment.
Environ Pollut
October 2021
Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu, 210009, China.
Article Synopsis
- - Ambient particulate matter (APM) poses risks to human vascular endothelial cells by causing abnormal autophagy, but the reasons for this autophagosome buildup remain unclear.
- - The study examined how different exposure times to urban particulate matter (PM SRM1648a) affect autophagic processes in EA.hy926 endothelial cells, discovering that the response varies based on exposure duration.
- - Key findings indicate that while initial exposure leads to increased autophagic activity, longer exposure results in dysfunctional autophagy due to lysosomal imbalance, highlighting the importance of maintaining lysosomal health to protect against APM-induced cell damage.
Systems level profiling of chemotherapy-induced stress resolution in cancer cells reveals druggable trade-offs.
Proc Natl Acad Sci U S A
April 2021
Cancer Cell Protein Metabolism, Department of Immunology and Inflammation, Imperial College London, London W12 0NN, United Kingdom;
Cancer cells can survive chemotherapy-induced stress, but how they recover from it is not known. Using a temporal multiomics approach, we delineate the global mechanisms of proteotoxic stress resolution in multiple myeloma cells recovering from proteasome inhibition. Our observations define layered and protracted programs for stress resolution that encompass extensive changes across the transcriptome, proteome, and metabolome.
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!