NEWS Within the frame of UCMR seminar series, Sascha Martens and Sabrina Büttner lecture on autophagy and lipophagy respectively.
Sascha Martens, University of Vienna, and Sabrina Büttner, Stockholm University
ImageprivatTime: 25 April 14:00-16:00
Venue: Lilla hörsalen (KB.E3.01), KBC
Sascha Martens, Max Perutz Labs, University of Vienna, Vienna BioCenter, Vienna, Austria
Autophagy is an intracellular lysosomal bulk degradation pathway that ensures cellular homeostasis by the removal of damaged and dangerous material from the cytoplasm. This is achieved by the sequestration of the cytoplasmic cargo material within double membraned organelles called autophagosomes. The selective sequestration of only specific cargo material is mediated by cargo receptors that link the cargo to the nascent autophagosomal membrane. How cargo selection, membrane nucleation and growth are coupled is unclear.
I will present our recent work on the cargo receptors and the autophagy machinery derived from in vitro reconstitution systems and cell biology. In particular, I will discuss how cargo receptors and the autophagy machinery act sequentially during cargo recognition, membrane nucleation and elongation to mediate the specific sequestration and subsequent degradation of cellular material.
More information about Sascha Marten and his lab
Sabrina Büttner, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University
Cellular adaptation to changing metabolic demands requires efficient communication between organelles and remodeling of subcellular structures. Membrane contact sites establish physical contact between organelles, serving as communication routes and important sites for metabolic adaptation in organisms ranging from yeast to humans. In yeast, a contact site that dynamically changes size and architecture in response to nutrient availability is the nucleus-vacuole junction (NVJ). NVJ connects the main anabolic and catabolic compartments by establishing proximity between the nuclear endoplasmic reticulum and the vacuole, the yeast lysosome. When nutrients are depleted, NVJs expand and coordinate distinct aspects of lipid metabolism, including the subcellular organization of lipid droplets (LDs). LDs are fat storage organelles critical for energy and lipid metabolism. Upon nutrient exhaustion, cells consume LDs via gradual lipolysis or via lipophagy, the en bloc uptake of LDs into the vacuole.
We show that LDs dock to the vacuolar membrane via a contact site that is required for lipophagy in yeast. The LD-localized LDO proteins carry an intrinsically disordered region that directly binds vacuolar Vac8 to form vCLIP, the vacuole-LD contact site. Nutrient limitation drives vCLIP formation, and its inactivation blocks lipophagy, resulting in impaired caloric restriction-induced longevity. We establish a functional link between lipophagy and NVJ-associated microautophagy, both requiring Vac8 to form respective contact sites upon metabolic stress. In sum, we identify the tethering machinery of vCLIP and find that Vac8 provides a platform for multiple and competing contact sites associated with autophagy.
