题 目：The Lysosome in Nutrient Sensing and Cellular Growth Control

主 讲：Roberto Zoncu 教授（加州大学伯克利分校）

时 间：2026年10月29日（周四）上午10:20-11:20

地 点：琳恩图书馆111报告厅

报告摘要：

The lysosome plays a central role in cellular homeostasis through its participation in autophagy and its physical and functional association with the master growth regulator, mechanistic target of rapamycin complex 1 (mTORC1) kinase. mTORC1 integrates signals from nutrients, hormones and energy to control the balance between cellular growth and repair programs. Nutrients, including cholesterol, drive the localization of the master growth regulator, mechanistic Target of Rapamycin Complex 1 (mTORC1) to the lysosomal membrane, where mTORC1 regulates its downstream programs. Cholesterol sensing by mTORC1 occurs upstream of the heterodimeric Rag guanosine triphosphatases (GTPases) via the lysosomal cholesterol sensor LYCHOS, and is negatively regulated by the cholesterol exporter, Niemann-Pick C1 (NPC1) protein. In NPC1-deleted cells, mTORC1 becomes dysregulated, leading to disruption of autophagy and mitochondrial function. These data implicate aberrant cholesterol-mTORC1 signaling as a candidate pathogenic driver in the neurodegenerative disease, Niemann-Pick type C (NPC), but the molecular mechanisms of mTORC1-dependent cellular dysfunction in NPC remain to be determined. I will present our recent effort to unravel lysosomal cholesterol sensing in neuronal models through a combination of imaging, organelle proteomics, bioinformatic analysis and functional assays. Moreover, I will discuss ongoing work exploring selective autophagy for targeted elimination of toxic cellular substrates via the lysosome.

嘉宾简介: 

Roberto Zoncu is Professor in the Molecular Therapeutics Division, Department of Molecular and Cell Biology, at UC Berkeley, where he serves as co-director of the Molecular Therapeutics Initiative.

Zoncu studied molecular biology at the University of Pisa and earned his PhD at the Yale School of Medicine. He joined UC Berkeley as an Assistant Professor in 2014, was promoted to Associate Professor with tenure in 2019, and to Full Professor in 2023.

The Zoncu lab investigates how nutrients regulate cellular growth and homeostasis via lysosomes. Combining advanced live-cell microscopy, in vitro biochemistry, and high-throughput profiling of proteins and metabolites, his team has revealed the lysosome as a central signaling node that relays nutrient availability to key pathways, including the master growth regulator mTORC1 kinase. The lab now explores the lysosome as a metabolic "command and control" center that (i) acts as a hub for nutrient sensing and signaling and (ii) governs the storage and delivery of key substrates to cellular metabolic pathways.

Prof. Zoncu’s achievements have been recognized by the NIH Director's New Innovator Award, the Pew-Stewart Scholarship for Cancer Research, the Damon Runyon–Rachleff Innovation Award, the Pew Innovation Award, and the Chan Zuckerberg Initiative "Metabolism Across Scales" Award.