Analysis of Mitochondrial Morphology and Function

线粒体形态和功能分析

基本信息

批准号：
7305891
负责人：
DENNIS R LA JEUNESSE
金额：
$ 20.93万
依托单位：
UNIVERSITY OF NORTH CAROLINA GREENSBORO
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-01-01 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7305891
关键词：
Alzheimer&apos s Disease Amyotrophic Lateral Sclerosis Antibodies Apical Apoptosis Biochemical Brain Calcium Cell Cycle Progression Cell Polarity Cell physiology Cholesterol Chromosomes Defect Disease Drosophila genus Drug or chemical Tissue Distribution Essential Genes Family Fat Body Food Gastrointestinal tract structure Genes Genetic Genetic Screening Goals Grant Homeostasis Human Kearns-Sayre syndrome Larva Lesion MELAS Maps Metaphase Mitochondria Molecular Morphology Movement Muscle Muscle Mitochondria Mutation Myopathy Neuropathy Numbers Organelles Organism Parkinson Disease Pathway interactions Phenotype Planet Mars Production Proteins Reporting Research Personnel Role Signal Transduction Structure Toxic Environmental Substances Training and Education Transport Vesicles Visceral cholesterol biosynthesis deletion analysis design human disease imaginal disc interest lipid biosynthesis lipid transport oxysterol binding protein research study

项目摘要

DESCRIPTION (provided by applicant): Mitochondria are dynamic organelles that are required for a variety of cellular functions including the production of ATP, apoptosis, lipid biosynthesis, the degradation of environmental toxins, and calcium homeostasis. Alteration to mitochondrial morphology and function has been associated with several human myopathies and neuropathies including Parkinson's, Kearns-Sayre syndrome and Amyotrophic Lateral Sclerosis. In a genetic screen of ~700 late larval/pupal lethal chromosomes, we have identified nine new genes that are required for proper mitochondrial morphology in the Drosophila visceral muscles. One of these new mitochondrial morphology genes is an essential gene: messy mitochondria. Besides its mitochondrial morphology phenotypes, mutations in messy mitochondria express a small/abnormal imaginal disc phenotype, defects in the movement of food along the alimentary canal and an extended larval period. Imaginal discs from larvae homozygous for a null messy mitochondria mutation have disrupted apical/basal polarity. We have mapped Messy mitochondria to the 96B4-B11 on the third chromosome and we have identified a molecular lesion associated with messy mitochondria in the Oxysterol binding protein gene. Oxysterols are intermediates in cholesterol degradation/biosynthetic pathways and have been implicated in a number of human diseases including Arthrosclerosis and Alzheimer's disease and are believed to be involved in a number of important signaling and biosynthetic pathways. Oxysterol binding proteins are a large family of well conserved proteins that are involved in a number of cellular processes including lipid transport, cell polarity, lipid biosynthesis and vesicle transport. The goal of this grant is to characterize the biochemical and cellular requirement for the messy mitochondria gene. This grant will be the first reported genetic characterization of an Oxysterol binding protein in a multicellular genetic organism. Given the interesting phenotypes associated with the messy mitochondria /Oxysterol binding protein gene, we expect that the results will be important for understanding mitochondrial morphology and other cellular processes involving Oxysterols and cholesterol. The goal of this project it to gain a better understanding of the fundamental role that mitochondrial morphology and function has in the cellular processes associated with a variety of human disorders including ALS, Parkinson's disease and MELAS. As AREA grant, this project has been designed to accommodate the training and education of undergraduate researchers.

描述（由申请人提供）：线粒体是多种细胞功能所需的动态细胞器，包括 ATP 的产生、细胞凋亡、脂质生物合成、环境毒素的降解和钙稳态。线粒体形态和功能的改变与多种人类肌病和神经病有关，包括帕金森病、卡恩斯-塞尔综合征和肌萎缩侧索硬化症。在对约 700 条晚期幼虫/蛹致死染色体的遗传筛选中，我们鉴定了果蝇内脏肌中适当线粒体形态所需的 9 个新基因。这些新的线粒体形态基因之一是必需基因：杂乱线粒体。除了线粒体形态表型外，杂乱线粒体的突变还表现出小/异常的成虫盘表型、食物沿消化道运动的缺陷以及幼虫期延长。来自纯合子幼虫的成虫盘因无效的杂乱线粒体突变而破坏了顶端/基底极性。我们已经将杂乱的线粒体定位到第三染色体上的 96B4-B11，并且我们已经在氧甾醇结合蛋白基因中鉴定出与杂乱的线粒体相关的分子损伤。氧甾醇是胆固醇降解/生物合成途径的中间体，与许多人类疾病有关，包括关节硬化症和阿尔茨海默氏病，并且被认为参与许多重要的信号传导和生物合成途径。氧甾醇结合蛋白是一个高度保守的蛋白质大家族，参与许多细胞过程，包括脂质转运、细胞极性、脂质生物合成和囊泡转运。这笔资助的目标是确定杂乱线粒体基因的生化和细胞需求。该资助将是首次报道多细胞遗传生物中氧甾醇结合蛋白的遗传特征。鉴于与杂乱的线粒体/氧甾醇结合蛋白基因相关的有趣表型，我们预计这些结果对于理解线粒体形态和涉及氧甾醇和胆固醇的其他细胞过程非常重要。该项目的目标是更好地了解线粒体形态和功能在与多种人类疾病（包括 ALS、帕金森病和 MELAS）相关的细胞过程中的基本作用。作为 AREA 拨款，该项目旨在适应本科研究人员的培训和教育。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Three new Drosophila markers of intracellular membranes.

三种新的果蝇细胞内膜标记。

DOI：
10.2144/04365st01
发表时间：
2004-05-01
期刊：
BioTechniques
影响因子：
2.7
作者：
D. LaJeunesse;Stephanie M Buckner;J. Lake;Charles Na;Am;a Pirt;a;Kathryn Fromson
通讯作者：
Kathryn Fromson

Epstein-Barr virus immediate-early proteins BZLF1 and BRLF1 alter mitochondrial morphology during lytic replication.

Epstein-Barr 病毒立即早期蛋白 BZLF1 和 BRLF1 在裂解复制过程中改变线粒体形态。