The Adenine Nucleotide Translocase: A Central Component of the Mitochondrial Permeability Transition Pore and Key Player in Cell Death

电压依赖性阴离子通道 线粒体通透性转换孔 蚂蚁 线粒体 腺嘌呤核苷酸 线粒体内膜 MPTP公司 细胞生物学 内膜 生物 化学 生物化学 程序性细胞死亡 生物物理学 腺嘌呤核苷酸转运体 细菌外膜 核苷酸 细胞凋亡 神经科学 生态学 多巴胺 大肠杆菌 多巴胺能 基因
作者
Andrew P. Halestrap,Catherine Brenner
出处
期刊:Current Medicinal Chemistry [Bentham Science]
卷期号:10 (16): 1507-1525 被引量:490
标识
DOI:10.2174/0929867033457278
摘要

In addition to its normal function, the adenine nucleotide translocase (ANT) forms the inner membrane channel of the mitochondrial permeability transition pore (MPTP). Binding of cyclophilin-D (CyPD) to its matrix surface (probably on Pro61 on loop 1) facilitates a calcium-triggered conformational change converting it from a specific transporter to a non-specific pore. The voltage dependent anion channel (VDAC) binds to the outer face of the ANT, at contact sites between the inner and outer membranes, and together VDAC, ANT and CyP-D probably represent the minimum MPTP configuration. The evidence for this is critically reviewed as is the structure and molecular mechanism of the carrier in its normal physiological mode. This provides helpful insights into MPTP regulation by adenine nucleotides, membrane potential and ANT ligands such as carboxyatractyloside and bongkrekic acid. Oxidative stress activates the MPTP by glutathionemediated cross-linking of Cys159 and Cys256 on matrix-facing loops of the ANT that inhibits ADP binding and enhances CyP-D binding. Molecular modeling of the loop containing the ADP binding site suggests an arrangement of aspartate and glutamate residues that may provide a calcium binding site. There are other proteins that may bind to the ANT, modulating MPTP opening and hence cell death. These included members of the Bax / Bcl-2 family (both oncoproteins and tumor suppressors) and viral proteins. Vpr from HIV-1 can bind to ANT and convert it into a pro-apoptotic pore, whereas vMIA from cytomegalovirus interacts to inhibit opening. Thus the ANT may provide a molecular link between physiopathological mechanisms of infection and the regulation of MPTP function and so represents a potential therapeutic target. Keywords: cyclophilin, voltage dependent anion channel, oxidative stress, carboxyatractyloside, bongkrekic acid, bax/bcl-2 family, viral infection, apoptosis
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
白介素-11发布了新的文献求助10
刚刚
刚刚
zxp完成签到 ,获得积分10
刚刚
1秒前
会撒娇的金鑫完成签到,获得积分20
2秒前
顺心的猪完成签到 ,获得积分10
3秒前
3秒前
VDC应助Jodie采纳,获得30
3秒前
落后火车发布了新的文献求助10
4秒前
自然浩阑完成签到,获得积分10
4秒前
zzzsss发布了新的文献求助10
5秒前
倩倩完成签到,获得积分10
7秒前
7秒前
7秒前
科研小赵发布了新的文献求助10
8秒前
8秒前
无花果应助十月二十采纳,获得10
8秒前
乐乐应助敦敦采纳,获得10
9秒前
leon完成签到,获得积分10
11秒前
MoL驳回了VDC应助
11秒前
Seven完成签到 ,获得积分10
11秒前
淡淡绿柏完成签到,获得积分10
11秒前
Coffee发布了新的文献求助10
12秒前
wjy完成签到,获得积分10
12秒前
丘比特应助为溪采纳,获得30
13秒前
13秒前
赘婿应助leon采纳,获得10
14秒前
L同学完成签到,获得积分20
14秒前
15秒前
大方大船完成签到,获得积分10
15秒前
迷路破茧完成签到,获得积分10
15秒前
李爱国应助倩倩采纳,获得10
16秒前
16秒前
18秒前
18秒前
Orange应助小白采纳,获得10
18秒前
Nicole发布了新的文献求助10
20秒前
科研小赵完成签到,获得积分10
20秒前
科研小白一枚完成签到,获得积分10
20秒前
20秒前
高分求助中
The late Devonian Standard Conodont Zonation 2000
Nickel superalloy market size, share, growth, trends, and forecast 2023-2030 2000
The Lali Section: An Excellent Reference Section for Upper - Devonian in South China 1500
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 800
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 800
Saponins and sapogenins. IX. Saponins and sapogenins of Luffa aegyptica mill seeds (black variety) 500
Fundamentals of Dispersed Multiphase Flows 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3260841
求助须知:如何正确求助?哪些是违规求助? 2901913
关于积分的说明 8318187
捐赠科研通 2571677
什么是DOI,文献DOI怎么找? 1397150
科研通“疑难数据库(出版商)”最低求助积分说明 653663
邀请新用户注册赠送积分活动 632213