AI Article Synopsis
- Mitochondria play a key role in metabolic processes necessary for cell health and growth.
- Researchers studied how human cells react to mitochondrial dysfunction by examining metabolomics in fibroblasts from patients with mitochondrial disorders and cancer cells with disrupted electron transport chains (ETC).
- The findings showed that ETC defects lower de novo purine synthesis while increasing purine salvage, highlighting a shift in metabolism, particularly in lung cancer cells expressing high levels of the enzyme HPRT1, which is crucial for purine salvage.
- Targeting HPRT1 makes cancer cells more sensitive to ETC inhibition, revealing a new potential weakness in tumors with low oxidative metabolism.
Article Abstract
Mitochondria house many metabolic pathways required for homeostasis and growth. To explore how human cells respond to mitochondrial dysfunction, we performed metabolomics in fibroblasts from patients with various mitochondrial disorders and cancer cells with electron transport chain (ETC) blockade. These analyses revealed extensive perturbations in purine metabolism, and stable isotope tracing demonstrated that ETC defects suppress de novo purine synthesis while enhancing purine salvage. In human lung cancer, tumors with markers of low oxidative mitochondrial metabolism exhibit enhanced expression of the salvage enzyme hypoxanthine phosphoribosyl transferase 1 (HPRT1) and high levels of the HPRT1 product inosine monophosphate. Mechanistically, ETC blockade activates the pentose phosphate pathway, providing phosphoribosyl diphosphate to drive purine salvage supplied by uptake of extracellular bases. Blocking HPRT1 sensitizes cancer cells to ETC inhibition. These findings demonstrate how cells remodel purine metabolism upon ETC blockade and uncover a new metabolic vulnerability in tumors with low respiration.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11240302 | PMC |
| http://dx.doi.org/10.1016/j.cmet.2024.05.014 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Tuning electronic structure and carrier transport properties through crystal orientation control in two-dimensional Dion-Jacobson phase perovskites.
Nano Converg
January 2025
Department of Physics, Yonsei University, Seoul, 03722, Republic of Korea.
Two-dimensional halide perovskites are attracting attention due to their structural diversity, improved stability, and enhanced quantum efficiency compared to their three-dimensional counterparts. In particular, Dion-Jacobson (DJ) phase perovskites exhibit superior structural stability compared to Ruddlesden-Popper phase perovskites. The inherent quantum well structure of layered perovskites leads to highly anisotropic charge transport and optical properties.
View Article and Find Full Text PDFThis study primarily investigated the mechanism of Astragalus polysaccharides(APS), a Chinese medicinal material, in regulating the Nrf2/SLC7A11/GPX4 signaling pathway to induce ferroptosis in ovarian cancer cells(Caov-3 and SKOV3 cells). Caov-3 and SKOV3 cells were divided into control(Vehicle) group, APS group, glutathione peroxidase 4 inhibitor(RSL3) group, and APS+RSL3 group. After 48 h of intervention, the activity and morphology of the cells in each group were observed.
View Article and Find Full Text PDFThe dual impact of tire wear microplastics on the growth and ecological interactions of duckweed Lemna minor.
Environ Pollut
January 2025
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia; Faculty of Mechanical Engineering, Brno University of Technology, Brno, Czech Republic. Electronic address:
Tire wear microplastics (TWMs) are continuously generated during driving and are subsequently released into the environment, where they pose potential risks to aquatic organisms. In this study, the effects of untreated, hydrated, and environmentally aged TWMs on the growth, root development, photosynthesis, electron transport system (ETS) activity, and energy-rich molecules of duckweed Lemna minor were investigated. The results indicated that untreated and aged TWMs have the most pronounced negative effects on Lemna minor, as evidenced by reduced growth and impaired root development.
View Article and Find Full Text PDFReductive stress: The key pathway in metabolic disorders induced by overnutrition.
J Adv Res
January 2025
The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:
Background: The balance of redox states is crucial for maintaining physiological homeostasis. For decades, the focus has been mainly on the concept of oxidative stress, which is involved in the mechanism of almost all diseases. However, robust evidence has highlighted that reductive stress, the other side of the redox spectrum, plays a pivotal role in the development of various diseases, particularly those related to metabolism and cardiovascular health.
View Article and Find Full Text PDFDecoupling Carrier Dynamics and Energy Transport in Ultrafast Near-Field Nanoscopy.
Nano Lett
January 2025
Laser Thermal Laboratory, Department of Mechanical Engineering, University of California, Berkeley, California 94720, United States.
Ultrafast near-field optical nanoscopy has emerged as a powerful platform to characterize low-dimensional materials. While analytical and numerical models have been established to account for photoexcited carrier dynamics, quantitative evaluation of the associated pulsed laser heating remains elusive. Here, we decouple the photocarrier density and temperature increase in near-field nanoscopy by integrating the two-temperature model (TTM) with finite-difference time-domain (FDTD) simulations.
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!