SLC25A48控制了线粒体胆进口和新陈代谢
Anthony R P Verkerke1, Xu Shi2, Mark Li1
1Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, and Howard Hughes Medical Institute, Boston, MA, USA.
Cell metabolism
|August 7, 2024
概括
线粒体蛋白SLC25A48对于将胆运输到细胞中至关重要,支持能量生产和细胞存活. 它的缺乏会损害线粒体功能,增加氧化应激.
科学领域:
- 线粒体生物学 线粒体生物学
- 细胞代谢的细胞代谢.
- 营养物质的运输 营养物质的运输
背景情况:
- 胆对细胞功能至关重要,但线粒体的运输机制尚不清楚.
- 线粒体胆进口对于合成关键代谢中间体至关重要.
研究的目的:
- 为了识别和描述负责线粒体胆运输的蛋白质.
- 阐明这种载体在细胞生物能学和生存中的作用.
主要方法:
- 对SLC25A48.48的基因鉴定和表征.
- 细胞测试测量胆吸收,线粒体呼吸和活性氧物种.
- 对具有SLC25A48.48基因变异的细胞进行分析.
主要成果:
- 一个线粒体载体的SLC25A48,调解了胆进口到线粒体矩阵.
- SLC25A48对于发热,呼吸和线粒体完整性至关重要.
- 失去SLC25A48会增加氧化应激,破坏脂质平衡,并损害细胞增殖.
结论:
- SLC25A48是线粒体胆代谢和细胞生物能学的关键调节剂.
- 功能障碍的SLC25A48与氧化应激和细胞存活能力受损有关,这对人类遗传变异和癌症有影响.
相关概念视频
Mitochondrial Protein Sorting
4.3K
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death. Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
4.3K
Protein Transport into the Inner Mitochondrial Membrane
3.7K
Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Transport of mitochondrial precursors across the TIM23 channel is driven by...
3.7K
Cholinergic Neurons: Neurotransmission
2.7K
Cholinergic neurotransmission involves the synthesis and the release of acetylcholine (ACh) in order to transmit nerve impulses across the synapse. The process begins with the synthesis of acetyl CoA, a precursor for ACh, from ATP, acetate, and coenzyme A in the mitochondria. Choline, another vital precursor, is transported inside the neuron through choline transporters, including high-affinity choline transporter CHT1, low-affinity choline transporter CTL1, and lower-affinity choline...
2.7K
Mitochondrial Precursor Proteins
2.6K
Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70 chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
Most of the mitochondrial...
2.6K
Translocation of Proteins into the Mitochondria
3.1K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.1K
Energy to Drive Translocation
2.1K
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Generally, polypeptides are unfolded by two distinct...
2.1K


