ArticleGenes & development2016
Autophagy provides metabolic substrates to maintain energy charge and nucleotide pools in Ras-driven lung cancer cells.
Article in Genes & development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 259 papers, 1 of them a synthesis that pooled it.
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Who cites it
259 citing papers in PubMed, 1 synthesis or guideline pooled it, 368 citations in OpenAlex.
- Global research and emerging trends in autophagy in lung cancer: a bibliometric and visualized study from 2013 to 2022.Frontiers in pharmacology · 2024Pooled it
- Lysosomal metabolism in pancreatic cancer and its crosstalk with host physiology.Genes & development · 2026Review
- Metabolism, autophagy, and cell death: The triangular axis in tumor survival and therapeutic resistance.Redox biology · 2026Review
- Myeloid differentiation-associated autophagy drives venetoclax resistance in AML.Research square · 2026Article
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- ER-mitochondria tether ML1 coordinates peripheral fission and wholesale mitophagy for plant adaptation to carbon starvation.Science advances · 2026Article
- An overview of circular RNAs in the regulation of autophagy in lung cancer.Discover oncology · 2026Review
- Hallmarks of the ageing lung: 10 years later.The European respiratory journal · 2026Review
- Article
- Regulated cell death programs shaping cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Article
- Loss of PIK3CA AllowsCells · 2026Article
- Autophagy in cancer-associated fibroblasts: its role in gastrointestinal cancers.Molecular cancer · 2026Review
- Telomere Crisis Shapes Cancer Evolution.Cold Spring Harbor perspectives in biology · 2026Review
- Loss of PIK3CA allowsbioRxiv : the preprint server for biology · 2026Article
- Integrating the hallmarks of cancer into autophagy: a perspective from underlying mechanisms to therapeutic strategies.Theranostics · 2026Review
- The role of energy deficit in autophagy failure in Parkinson's disease.Frontiers in aging neuroscience · 2026Review
- Unraveling autophagy-metabolism crosstalk in cancer: Molecular insights and therapeutic strategies.Theranostics · 2026Review
- Autophagy modulation in gynaecologic oncology: insights into immune regulation and therapeutic potential.Frontiers in immunology · 2026Review
- Metabolic immune checkpoints in cancer: how tumor-derived metabolites shape immunotherapy resistance.Frontiers in immunology · 2026Review
199 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
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Abstract
Autophagy degrades and is thought to recycle proteins, other macromolecules, and organelles. In genetically engineered mouse models (GEMMs) for Kras-driven lung cancer, autophagy prevents the accumulation of defective mitochondria and promotes malignancy. Autophagy-deficient tumor-derived cell lines are respiration-impaired and starvation-sensitive. However, to what extent their sensitivity to starvation arises from defective mitochondria or an impaired supply of metabolic substrates remains unclear. Here, we sequenced the mitochondrial genomes of wild-type or autophagy-deficient (Atg7(-/-)) Kras-driven lung tumors. Although Atg7 deletion resulted in increased mitochondrial mutations, there were too few nonsynonymous mutations to cause generalized mitochondrial dysfunction. In contrast, pulse-chase studies with isotope-labeled nutrients revealed impaired mitochondrial substrate supply during starvation of the autophagy-deficient cells. This was associated with increased reactive oxygen species (ROS), lower energy charge, and a dramatic drop in total nucleotide pools. While starvation survival of the autophagy-deficient cells was not rescued by the general antioxidant N-acetyl-cysteine, it was fully rescued by glutamine or glutamate (both amino acids that feed the TCA cycle and nucleotide synthesis) or nucleosides. Thus, maintenance of nucleotide pools is a critical challenge for starving Kras-driven tumor cells. By providing bioenergetic and biosynthetic substrates, autophagy supports nucleotide pools and thereby starvation survival.
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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.