铁和线粒体ROS是SARS-CoV-2引起的肝细胞死亡的核心原因
Cintia Cevallos1, Patricio Jarmoluk1, Franco Sviercz1
1Universidad de Buenos Aires (UBA), Consejo de Investigaciones Científicas y Técnicas (CONICET), Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Laboratorio de Inmunopatogénesis Viral, Buenos Aires, Argentina.
Frontiers in cellular and infection microbiology
|August 27, 2025
概括
严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 感染通过破坏线粒体功能和促进细胞死亡的一种类型 - - 铁亡,导致肝损伤. 针对线粒体反应性氧物种和铁代谢可能为COVID-19肝损伤提供治疗策略.
科学领域:
- 肝病学
- 病毒学
- 细胞生物学
背景情况:
- COVID-19主要是一种呼吸系统疾病,与肝脏损伤越来越相关.
- 造成SARS-CoV-2肝细胞损伤的机制尚未完全理解.
- 线粒体功能障碍,氧化应激和受调的细胞死亡都与COVID-19的发病有关.
研究的目的:
- 研究SARS-CoV-2感染对肝细胞线粒体功能,脂质代谢和细胞死亡途径的影响.
- 为了比较祖先武汉和Omicron BA.5变异对肝细胞的影响.
- 确定COVID-19相关肝损伤的潜在治疗点.
主要方法:
- Huh7.5肝细胞感染了武汉或Omicron BA.5 SARS-CoV-2 变种.
- 使用RT- qPCR,核囊蛋白检测和传染性颗粒定位进行了病毒复制评估.
- 使用各种测定和抑制剂分析了线粒体功能,脂质新陈代谢和细胞死亡 (亡,热亡,铁亡).
主要成果:
- 这两种SARS-CoV-2变种都感染了肝细胞,表现出不同的复制模式.
- 感染导致线粒体碎片化,线粒体活性氧物种 (mROS) 增加和脂质滴积累.
- 铁死被确定为主要的细胞死亡机制,具有上调的ACE2和TfR1表达. mROS 清除抑制病毒复制.
结论:
- SARS-CoV-2 破坏肝细胞线粒体平衡和脂质代谢,诱导铁死.
- 铁是COVID-19中病毒诱导的肝细胞病理的一个关键因素.
- 线粒体ROS和铁代谢代表了COVID-19相关的肝损伤的潜在治疗目标.
更多相关视频
相关概念视频
01:16Necrosis
4.8K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
4.8K
01:46Electron Transport Chain: Complex I and II
15.0K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
15.0K
01:30Overview of Cell Death
7.7K
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
7.7K
01:30The Electron Transport Chain
17.3K
The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
17.3K
01:45Mitochondrial Membranes
12.3K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
12.3K
01:24Peroxisomes
14.3K
Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
14.3K