Suppr超能文献

线粒体丙酮酸载体在癌细胞代谢和肿瘤发生中的重要性。

The Importance of Mitochondrial Pyruvate Carrier in Cancer Cell Metabolism and Tumorigenesis.

作者信息

Ruiz-Iglesias Ainhoa, Mañes Santos

机构信息

Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB/CSIC), 28049 Madrid, Spain.

出版信息

Cancers (Basel). 2021 Mar 24;13(7):1488. doi: 10.3390/cancers13071488.

Abstract

Pyruvate is a key molecule in the metabolic fate of mammalian cells; it is the crossroads from where metabolism proceeds either oxidatively or ends with the production of lactic acid. Pyruvate metabolism is regulated by many enzymes that together control carbon flux. Mitochondrial pyruvate carrier (MPC) is responsible for importing pyruvate from the cytosol to the mitochondrial matrix, where it is oxidatively phosphorylated to produce adenosine triphosphate (ATP) and to generate intermediates used in multiple biosynthetic pathways. MPC activity has an important role in glucose homeostasis, and its alteration is associated with diabetes, heart failure, and neurodegeneration. In cancer, however, controversy surrounds MPC function. In some cancers, MPC upregulation appears to be associated with a poor prognosis. However, most transformed cells undergo a switch from oxidative to glycolytic metabolism, the so-called Warburg effect, which, amongst other possibilities, is induced by MPC malfunction or downregulation. Consequently, impaired MPC function might induce tumors with strong proliferative, migratory, and invasive capabilities. Moreover, glycolytic cancer cells secrete lactate, acidifying the microenvironment, which in turn induces angiogenesis, immunosuppression, and the expansion of stromal cell populations supporting tumor growth. This review examines the latest findings regarding the tumorigenic processes affected by MPC.

摘要

丙酮酸是哺乳动物细胞代谢命运中的关键分子;它是代谢走向氧化或最终产生乳酸的十字路口。丙酮酸代谢由许多共同控制碳通量的酶调节。线粒体丙酮酸载体(MPC)负责将丙酮酸从细胞质转运到线粒体基质,在那里它被氧化磷酸化以产生三磷酸腺苷(ATP)并生成用于多种生物合成途径的中间体。MPC活性在葡萄糖稳态中起重要作用,其改变与糖尿病、心力衰竭和神经退行性变有关。然而,在癌症中,MPC的功能存在争议。在某些癌症中,MPC上调似乎与预后不良有关。然而,大多数转化细胞会从氧化代谢转变为糖酵解代谢,即所谓的瓦伯格效应,这在其他可能性中是由MPC功能障碍或下调诱导的。因此,MPC功能受损可能会诱导具有强大增殖、迁移和侵袭能力的肿瘤。此外,糖酵解癌细胞分泌乳酸,使微环境酸化,进而诱导血管生成、免疫抑制以及支持肿瘤生长的基质细胞群体的扩张。本综述探讨了有关MPC影响肿瘤发生过程的最新发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1a2/8037430/b5233e074f3c/cancers-13-01488-g001.jpg

相似文献

1
The Importance of Mitochondrial Pyruvate Carrier in Cancer Cell Metabolism and Tumorigenesis.
Cancers (Basel). 2021 Mar 24;13(7):1488. doi: 10.3390/cancers13071488.
2
Tumor microenvironment and metabolic synergy in breast cancers: critical importance of mitochondrial fuels and function.
Semin Oncol. 2014 Apr;41(2):195-216. doi: 10.1053/j.seminoncol.2014.03.002. Epub 2014 Mar 5.
3
The mitochondrial pyruvate carrier in health and disease: To carry or not to carry?
Biochim Biophys Acta. 2016 Oct;1863(10):2436-42. doi: 10.1016/j.bbamcr.2016.01.017. Epub 2016 Jan 26.
4
The mitochondrial pyruvate carrier at the crossroads of intermediary metabolism.
Am J Physiol Endocrinol Metab. 2022 Jul 1;323(1):E33-E52. doi: 10.1152/ajpendo.00074.2022. Epub 2022 May 30.
5
Heart failure-emerging roles for the mitochondrial pyruvate carrier.
Cell Death Differ. 2021 Apr;28(4):1149-1158. doi: 10.1038/s41418-020-00729-0. Epub 2021 Jan 20.
9
The mitochondrial pyruvate carrier mediates high fat diet-induced increases in hepatic TCA cycle capacity.
Mol Metab. 2017 Nov;6(11):1468-1479. doi: 10.1016/j.molmet.2017.09.002. Epub 2017 Sep 18.
10
Mitochondrial pyruvate carrier function determines cell stemness and metabolic reprogramming in cancer cells.
Oncotarget. 2017 Jul 11;8(28):46363-46380. doi: 10.18632/oncotarget.18199.

引用本文的文献

2
DHODH Blockade Induces Ferroptosis in Neuroblastoma by Modulating the Mevalonate Pathway.
Mol Cell Proteomics. 2025 Jun 11;24(7):101014. doi: 10.1016/j.mcpro.2025.101014.
6
Structures and mechanism of the human mitochondrial pyruvate carrier.
Nature. 2025 May;641(8061):258-265. doi: 10.1038/s41586-025-08873-8. Epub 2025 Mar 18.
7
A Mathematical Exploration of SDH-b Loss in Chromaffin Cells.
Bull Math Biol. 2025 Mar 13;87(4):53. doi: 10.1007/s11538-025-01427-z.
9
The "Culture" of Organs: A Holistic Theory on the Origins of the Cancer Tissue Environment.
Life (Basel). 2024 Dec 7;14(12):1622. doi: 10.3390/life14121622.

本文引用的文献

1
The pyruvate-lactate axis modulates cardiac hypertrophy and heart failure.
Cell Metab. 2021 Mar 2;33(3):629-648.e10. doi: 10.1016/j.cmet.2020.12.003. Epub 2020 Dec 16.
3
Blocking mitochondrial pyruvate import in brown adipocytes induces energy wasting via lipid cycling.
EMBO Rep. 2020 Dec 3;21(12):e49634. doi: 10.15252/embr.201949634. Epub 2020 Dec 4.
4
Sequence Features of Mitochondrial Transporter Protein Families.
Biomolecules. 2020 Nov 28;10(12):1611. doi: 10.3390/biom10121611.
6
Insights on the Quest for the Structure-Function Relationship of the Mitochondrial Pyruvate Carrier.
Biology (Basel). 2020 Nov 19;9(11):407. doi: 10.3390/biology9110407.
7
Immuno-priming durvalumab with bevacizumab in HER2-negative advanced breast cancer: a pilot clinical trial.
Breast Cancer Res. 2020 Nov 11;22(1):124. doi: 10.1186/s13058-020-01362-y.
8
Lactate in the Tumor Microenvironment: An Essential Molecule in Cancer Progression and Treatment.
Cancers (Basel). 2020 Nov 3;12(11):3244. doi: 10.3390/cancers12113244.
9
Targeting Metabolic Plasticity and Flexibility Dynamics for Cancer Therapy.
Cancer Discov. 2020 Dec;10(12):1797-1807. doi: 10.1158/2159-8290.CD-20-0844. Epub 2020 Nov 2.
10
The Warburg Effect 97 Years after Its Discovery.
Cancers (Basel). 2020 Sep 30;12(10):2819. doi: 10.3390/cancers12102819.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验