{"id":537,"title":"Cancer cells differentially modulate mitochondrial respiration to alter redox state and enable biomass synthesis in nutrient-limited environments","title_zh":"癌细胞通过差异性调节线粒体呼吸改变氧化还原状态并在营养受限环境中支持生物量合成","url":"https://doi.org/10.7554/elife.107123.3","doi":"10.7554/elife.107123.3","pmid":null,"journal":"eLife","kind":"paper","lang":"en","published_at":"2026-11-04T00:00:00+00:00","fetched_at":"2026-11-08T03:45:22+00:00","authors":["Sarah M Chang","Muhammad Bin Munim","Sonia E Trojan","Huel Cox","Anna Shevzov-Zebrun","Keene L Abbott","Renee Chang","Matthew G Vander Heiden"],"primary_topic":"repro-aging","topics":[{"slug":"repro-aging","score":5.0,"hits":["mitochondrial","nad+"]}],"topic_score":5.0,"preference_score":0.0,"preference_labels":[],"llm_score":52.0,"final_score":58.0,"score_dims":{"novelty":76,"rigor":74,"impact":22,"relevance":12,"translation":14},"recommend_reason":"该文在肿瘤代谢与营养限制机制上有一定新颖性，但研究对象为癌细胞，与生殖医学、辅助生殖及胚胎多组学核心问题直接关联很低，不建议作为生殖领域每日必读。","keywords":["线粒体呼吸","NAD+/NADH比值","丝氨酸代谢","营养限制","癌细胞增殖"],"selected":0,"story_id":67,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"crossref-cns","source_name":"Crossref · CNS 与大子刊新上线（领域过滤）","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"elife","journal_tier":"general-top","journal_if":6.4,"is_mock":false,"summary_zh":"该研究以癌细胞为对象，探讨营养受限条件下NAD+/NADH比值的调控机制。研究发现，部分癌细胞在丝氨酸剥夺时通过增强线粒体呼吸提高NAD+/NADH比值，进而促进丝氨酸合成与增殖，且不依赖丝氨酸合成酶表达；脂质剥夺也可在部分细胞中经线粒体呼吸升高NAD+/NADH，若同时缺脂则可改善缺丝氨酸环境下的增殖。研究提示，营养剥夺诱导的线粒体呼吸变化以细胞特异方式影响氧化性生物量合成与增殖。","summary":"The cell NAD+/NADH ratio can constrain biomass synthesis and influence proliferation in nutrient-limited environments. However, which cell processes regulate the NAD+/NADH ratio is not known. Here, we find that some cancer cells elevate the NAD+/NADH ratio in response to serine deprivation by increasing mitochondrial respiration. Cancer cells that elevate mitochondrial respiration have higher serine production and proliferation in serine-limiting conditions than cells with no mitochondrial respiration response, independent of serine synthesis enzyme expression. Increases in mitochondrial respiration and the NAD+/NADH ratio promote serine synthesis regardless of whether serine is environmentally limiting. Lipid deprivation can increase the NAD+/NADH ratio via mitochondrial respiration in some cells, including cells that do not increase respiration following serine deprivation. Thus, in cancer cells where lipid depletion raises the NAD+/NADH ratio, proliferation in serine-depleted environments improves when lipids are also depleted. Taken together, these data suggest that changes in mitochondrial respiration in response to nutrient deprivation can influence the NAD+/NADH ratio in a cell-specific manner to impact oxidative biomass synthesis and proliferation. Given the complexity of tumor microenvironments, this work provides a metabolic framework for understanding how levels of more than one environmental nutrient affect cancer cell proliferation.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}