癌症中酸脱酶损失的代谢影响
Adam Chatoff1,2, Daniel S Kantner1, Nathaniel W Snyder1,2
1Aging + Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, USA.
Journal of cellular physiology
|July 21, 2025
概括
酸脱酶 (SDH) 对于细胞能量生产至关重要,并起到瘤抑制作用. 缺少SDH会扰乱新陈代谢,从而造成可用于治疗癌症和神经代谢障碍的脆弱性.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
背景情况:
- 酸脱酶 (SDH) 是一种关键的酶,在电子运输链中作为复合II,并在三碳酸循环中发挥关键作用.
- SDH是一个由SDHA,SDHB,SDHC和SDHD子单元组成的异构四重体复合体,其组装因子SDHAF1和SDHAF2促进了它的线粒体定位和功能.
- 该酶在新陈代谢中的双重作用及其作为瘤抑制剂的功能强调了其在正常生理学和疾病中的重要性.
研究的目的:
- 审查SDH在细胞代谢中的多方面的作用.
- 为了阐明SDH缺乏的代谢和蛋白质化学后果.
- 为了确定SDH缺乏细胞的潜在治疗漏洞,用于疾病治疗.
主要方法:
- 文献综述侧重于SDH功能,缺乏和相关疾病.
- 在SDH缺乏状态下对代谢重新连接和蛋白质组变化的分析.
- 探索针对代谢脆弱性的治疗策略.
主要成果:
- SDH 缺乏导致了显著的代谢重编程.
- SDH功能的丧失与各种癌症的瘤发生有关,包括色细胞瘤和清细胞细胞癌.
- 缺少SDH也会导致非新发性疾病,如利氏综合征.
结论:
- 了解SDH在新陈代谢和疾病中的作用对于基础和转化研究至关重要.
- 由SDH缺乏引起的代谢脆弱性是有前途的治疗点.
- 针对这些弱点可以为缺乏SDH的癌症和神经代谢障碍提供新的治疗策略.
相关概念视频
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
02:53Adaptive Mechanisms in Cancer Cells
5.9K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.9K
01:12Loss of Tumor Suppressor Gene Functions
5.1K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.1K
02:49Cancer Therapies
8.0K
Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
8.0K
02:56Treatment Resistant Cancers
3.4K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.4K
03:03mTOR Signaling and Cancer Progression
3.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.9K