Molecular mechanisms of intra- and inter-cellular fatty acid trafficking

细胞内和细胞间脂肪酸运输的分子机制

• 批准号: 10587303
• 负责人: Sarah Cohen
• 金额: $ 11.67万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10587303
• 关键词: Aging; Biological; Cell Aging; Cells; Communication; Disease; Endoplasmic Reticulum; Epigenetic Process; Fatty Acids; Genomic Instability; Golgi Apparatus; Health; Image; Lipids; Lysosomes; Mitochondria; Modeling; Molecular; Morphology; Organelles; Process; Shapes; Speed; Testing; cell type; detection of nutrient; exhaustion; imaging modality; intercellular communication; live cell imaging; mitochondrial dysfunction; novel; peroxisome; proteostasis; stem cells; telomere; trafficking

ABSTRACT The biological hallmarks of aging have outlined multiple cellular and molecular processes that contribute to aging. The hallmarks of aging include genomic instability; telomere attrition; epigenetic alterations; loss of proteostasis; deregulated nutrient sensing; mitochondrial dysfunction; cellular senescence; stem cell exhaustion; and altered intercellular communication. These processes have been studied primarily in isolation from each other. However, many of these processes span multiple cellular organelles or occur at the intersection between organelles. We will use multispectral imaging to systematically investigate the morphology and dynamics of six organelles simultaneously in live cells, as a method for imaging organelle communication in relation to the hallmarks of aging. The organelles we will image include endoplasmic reticulum, Golgi, lysosomes, mitochondria, peroxisomes, and lipid droplets. In aim 1, we will quantify organelle number, size, shape, speed, contacts with other organelles, and distribution (the “organelle signature”), in multiple cell types at baseline. In aim 2, we will test how organelle morphodynamics change during replicative aging. Together, these studies will identify novel forms of organelle communication impacting the hallmarks of aging.

抽象的 衰老的生物学标志概述了多个细胞和分子过程 有助于衰老。衰老的标志包括基因组不稳定性；端粒损耗； 表观遗传改变；失去蛋白质抑制剂；放松管制营养感；线粒体 功能障碍；细胞感应；干细胞耗尽；并改变了细胞间沟通。 这些过程主要是彼此隔离的。但是，很多 这些过程跨越多个细胞器或发生在 细胞器。我们将使用多光谱成像系统地研究形态和 仅在活细胞中的六个细胞器的动力学，作为成像细胞器的一种方法 与衰老标志有关的沟通。我们将形象的细胞器包括 内质网，高尔基体，溶酶体，线粒体，过氧化物体和脂质液滴。 1，我们将量化细胞器的数量，大小，形状，速度，与其他细胞器的接触，以及 分布（“细胞器签名”），基线时多种细胞类型。在AIM 2中，我们将测试 在复制衰老过程中，细胞器形态动力学如何变化。这些研究将在一起 确定细胞器交流的新型形式，影响衰老的标志。