Spatial Organization of the Mitochondrial Inner Membrane
线粒体内膜的空间组织
基本信息
- 批准号:10469391
- 负责人:
- 金额:$ 41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-01 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAlzheimer&aposs DiseaseArchitectureCell RespirationCell physiologyCellsComplexCrista ampullarisDefectDevelopmentDiseaseElementsFutureGenerationsGoalsHomeostasisHumanInner mitochondrial membraneIonsLeadLinkMembraneMitochondriaMolecularMorphogenesisMorphologyNeurodegenerative DisordersNucleotidesOrganellesOxidative PhosphorylationParkinson DiseasePhenotypePhospholipidsPositioning AttributeProductionResearchRespirationRoleSiteSystemTherapeuticWorkYeastsamino acid metabolismgenetic approachhuman diseaseinsightmitochondrial dysfunctionmitochondrial membranenovelprograms
项目摘要
Project Summary
Mitochondria are double-membrane bound organelles that perform many crucial cellular functions, including
nucleotide and amino acid metabolism, cellular phospholipid and ion homeostasis, and their most notorious
function, generation of cellular energy via oxidative phosphorylation. Mitochondrial form and function are tightly
linked. The ability of the organelle to efficiently perform respiration depends on the correct spatial organization
of the mitochondrial inner membrane into elaborately shaped morphological domains, including cristae, the
hallmark of the organelle. Cristae morphology defects lead to reduced cellular respiration and is a phenotypic
consequence of a number of diseases, including neurodegenerative disorders such as Alzheimer’s and
Parkinson’s Disease. Despite their importance, we have minimal mechanistic understanding of how cristae are
formed and organized within the organelle. Recently, the Mitochondrial Contact Site and Cristae Organizing
System (MICOS) complex was identified as a master regulator of spatial organization of mitochondria. I
previously determined that MICOS is organized into two non-redundant subcomplexes that independently
assemble and localize to cristae junctions, a key structural element of the mitochondrial inner membrane.
Despite our progress, we have minimal mechanistic understanding of how MICOS contributes to the number,
position, and morphogenesis of cristae membranes. In the next five years, our goal is to address these deficits
by exploring the molecular basis of MICOS function in yeast cells and, using candidate and forward genetic
strategies, determine how MICOS is regulated to fine tune cristae architecture in human cells. This work will
lead to insight into the spatial organization of mitochondria and the form-function relationship of the organelle,
provide the basis for the future development of my research program, and give us molecular insight into the
disorganization of mitochondrial membranes that occurs as a consequence of a number of human diseases.
项目摘要
线粒体是双膜结合的细胞器,执行许多重要的细胞功能,包括
核苷酸和氨基酸代谢,细胞磷脂和离子稳态,以及它们最臭名昭著的
功能,通过氧化磷酸化产生细胞能量。线粒体的形态和功能
有联系细胞器有效进行呼吸的能力取决于正确的空间组织
线粒体内膜的细胞分裂成精心塑造的形态结构域,包括嵴,
细胞器的标志嵴形态缺陷导致细胞呼吸减少,是一种表型
许多疾病的后果,包括神经退行性疾病,如阿尔茨海默氏症和
帕金森氏症尽管它们很重要,但我们对嵴是如何形成的机械理解很少。
在细胞器内形成和组织。最近,线粒体接触位点和嵴组织
系统(MICOS)复合物被确定为线粒体空间组织的主要调节因子。我
先前确定MICOS被组织成两个非冗余子复合体,
组装并定位于嵴连接处,这是线粒体内膜的关键结构元件。
尽管我们取得了进展,但我们对MICOS如何对数字做出贡献的机械理解很少,
嵴膜的位置和形态发生。在未来五年,我们的目标是解决这些赤字
通过探索酵母细胞中MICOS功能的分子基础,并使用候选和正向遗传学方法,
战略,确定如何MICOS是调节微调嵴结构在人类细胞。这项工作将
导致深入了解线粒体的空间组织和细胞器的形式-功能关系,
为我的研究计划的未来发展提供了基础,并让我们从分子上深入了解
由于许多人类疾病而发生的线粒体膜的紊乱。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jonathan R. Friedman其他文献
Compositionally unique mitochondria in filopodia support cellular migration
丝状伪足中具有成分独特的线粒体支持细胞迁移。
- DOI:
10.1016/j.cub.2025.01.062 - 发表时间:
2025-03-24 - 期刊:
- 影响因子:7.500
- 作者:
Madeleine Marlar-Pavey;Daniel Tapias-Gomez;Marcel Mettlen;Jonathan R. Friedman - 通讯作者:
Jonathan R. Friedman
Comparison of predicted and experimentally determined secondary structure of adenyl kinase
预测和实验确定的腺苷激酶二级结构的比较
- DOI:
10.1038/250140a0 - 发表时间:
1974 - 期刊:
- 影响因子:64.8
- 作者:
Georg E. Schulz;C. D. Barry;Jonathan R. Friedman;P. Y. Chou;G. Fasman;Alexei V. Finkelstein;V. Lim;Oleg B. Ptitsyn;E. A. Kabat;Taite Wu;Michael Levitt;Barry Robson;K. Nagano - 通讯作者:
K. Nagano
The effect of uniaxial pressure on the magnetic anisotropy of the Mn12-Ac single-molecule magnet
单轴压力对Mn12-Ac单分子磁体磁各向异性的影响
- DOI:
10.1209/0295-5075/102/47008 - 发表时间:
2013 - 期刊:
- 影响因子:0
- 作者:
James Atkinson;James Atkinson;K. Park;C. Beedle;D. N. Hendrickson;Y. Myasoedov;E. Zeldov;Jonathan R. Friedman;Jonathan R. Friedman - 通讯作者:
Jonathan R. Friedman
Jonathan R. Friedman的其他文献
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{{ truncateString('Jonathan R. Friedman', 18)}}的其他基金
Spatial Organization of the Mitochondrial Inner Membrane
线粒体内膜的空间组织
- 批准号:
10229557 - 财政年份:2020
- 资助金额:
$ 41万 - 项目类别:
Diversity Supplement for Spatial Organization of the Mitochondrial Inner Membrane
线粒体内膜空间组织的多样性补充
- 批准号:
10357501 - 财政年份:2020
- 资助金额:
$ 41万 - 项目类别:
Spatial Organization of the Mitochondrial Inner Membrane
线粒体内膜的空间组织
- 批准号:
10674219 - 财政年份:2020
- 资助金额:
$ 41万 - 项目类别:
Spatial Organization of the Mitochondrial Inner Membrane
线粒体内膜的空间组织
- 批准号:
10683127 - 财政年份:2020
- 资助金额:
$ 41万 - 项目类别:
Spatial Organization of the Mitochondrial Inner Membrane
线粒体内膜的空间组织
- 批准号:
10026824 - 财政年份:2020
- 资助金额:
$ 41万 - 项目类别:
Spatial Organization of the Mitochondrial Inner Membrane
线粒体内膜的空间组织
- 批准号:
10467263 - 财政年份:2020
- 资助金额:
$ 41万 - 项目类别:
Regulation of Mitochondrial Inner Membrane Organization
线粒体内膜组织的调控
- 批准号:
9334933 - 财政年份:2016
- 资助金额:
$ 41万 - 项目类别:
Regulation of mitochondrial inner membrane organization
线粒体内膜组织的调节
- 批准号:
9606265 - 财政年份:2016
- 资助金额:
$ 41万 - 项目类别:
Regulation of Mitochondrial Inner Membrane Organization
线粒体内膜组织的调控
- 批准号:
9162338 - 财政年份:2016
- 资助金额:
$ 41万 - 项目类别: