<br>线粒体活性氧稳态需要醚磷脂,Nature Communications

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线粒体活性氧稳态需要醚磷脂
Nature Communications ( IF 14.7 ) Pub Date : 2023-04-17 , DOI: 10.1038/s41467-023-37924-9
Ziheng Chen ₁ , I-Lin Ho ₁ , Melinda Soeung ₁ , Er-Yen Yen ₁ , Jintan Liu ₁ , Liang Yan ₂ , Johnathon L Rose _{1,

3} , Sanjana Srinivasan _{1,

3} , Shan Jiang ₃ , Q Edward Chang ₄ , Ningping Feng ₅ , Jason P Gay ₅ , Qi Wang ₆ , Jing Wang ₆ , Philip L Lorenzi ₆ , Lucas J Veillon ₆ , Bo Wei ₆ , John N Weinstein _{6,

7} , Angela K Deem ₃ , Sisi Gao ₁ , Giannicola Genovese _{1,

8} , Andrea Viale ₁ , Wantong Yao ₉ , Costas A Lyssiotis _{10,

11,

12} , Joseph R Marszalek _{3,

5} , Giulio F Draetta _{1,

2} , Haoqiang Ying ₂

Affiliation

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Translational Research to AdvanCe Therapeutics and Innovation in ONcology (TRACTION), The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
The Oncology Research for Biologics and Immunotherapy Translation (ORBIT), The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, University of Texas, Houston, TX, USA.
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA.
University of Michigan Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, 48109, USA.

线粒体是生物能学、氧化还原稳态和合成代谢途径通过紧密协调的代谢物流整合的枢纽。线粒体代谢对肿瘤生长和治疗耐药的贡献是显而易见的，但针对线粒体代谢的药物在临床上却屡屡失败。我们对胰腺导管腺癌 (PDAC) 的研究发现，细胞和线粒体脂质组成会影响癌细胞对电子传递链复合物 I 的药理抑制的敏感性。对患者来源的 PDAC 模型的分析表明，单不饱和脂肪酸 (MUFA) 和 MUFA 连接的醚磷脂在维持 ROS 稳态中发挥着关键作用。我们证明醚磷脂支持线粒体超复合物组装和 ROS 产生；因此，阻断从头开始的醚磷脂生物合成，通过诱导线粒体ROS和脂质过氧化，使PDAC细胞对复合物I抑制敏感。这些数据表明醚磷脂是线粒体氧化还原控制的调节剂，有助于提高 PDAC 细胞对复合物 I 抑制的敏感性。

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更新日期：2023-04-18

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