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.

摘要