Intracellular vesicle trafficking in senescent cells role of the Golgi complex?

National Institute On Aging

Investigators

Abstract

The accumulation of senescent cells with age is widely recognized as a major contributor to aging and age-related diseases. Abnormalities of multiple organelles contribute to the functional deficiency exhibited by senescent cells. The Golgi apparatus is a central organelle governing intracellular vesicle trafficking and secretion; defects in Golgi structure in senescent cells may affect intracellular transport and production of key proteins. In a recent screen, we found that proteins in the Golgi COPI intracellular vesicle trafficking complex were important for the uptake of extracellular vesicles. As these factors were decreased in senescent fibroblasts, we hypothesized that the altered morphology of Golgi in senescent cells may affect COPI vesicle trafficking and consequently EV uptake and secretion. Using established models of fibroblast senescence and leveraging the expertise in Golgi biology and senescent-cell proteomics present in NIA IRP, we propose to perform proteomic and transcriptomic characterization of the Golgi apparatus. We will then investigate the composition of Golgi vesicles to better understand Golgi-mediated processing and transport in the senescence phenotype. Finally, we will study the effect of silencing COPI genes on Golgi organization and proinflammatory cytokine production, including how Golgi influences the secretory phenotype of senescent cells.