Biology subjects

Baumann, V.

Publications and source records attributed to Baumann, V..

3 recordsLinked to original sources

bioRxiv2026

Activation of the bridge-like lipid transfer protein Atg2 by Atg1-mediated phosphorylation

Bridge-like lipid transfer proteins (BLTPs) have emerged as major contributors to lipid flux and thus cellular organization. BLTPs harbor a hydrophobic channel connecting two membranes to enable the bulk flow of lipids between them. The regulation of BLTPs is incompletely understood. Employing in vitro reconstitution, molecular dynamics simulations, and cell biology, we discovered that the BLTP Atg2, which mediates lipid transfer during autophagosome biogenesis, is activated by the Atg1 kinase. Atg1 phosphorylates two serines in the N-terminal region of Atg2. This triggers membrane binding and opening of the channel to enable lipid transfer. The Atg1 kinase complex is localized to the endoplasmic reticulum through binding of its Atg13 subunit to the VAP protein Scs2. Phosphorylated Atg2 can subsequently establish contacts with Atg9 vesicles. Our study delineates a pathway for the Atg1 kinase mediated activation of the BLTP Atg2 to establish membrane contact site formation and lipid flux.

cell biology↗

bioRxiv2023

Faa1 membrane binding drives positive feedback in autophagosome biogenesis via fatty acid activation

Autophagy serves as a stress response pathway by mediating the degradation of cellular material within lysosomes. In autophagy this material is encapsulated in double membrane vesicles termed autophagosomes, which form from precursors referred to as phagophores. Phagophores grow by lipid influx from the endoplasmic reticulum into Atg9-positive compartments and local lipid synthesis provides lipids for their expansion. How phagophore nucleation and expansion are coordinated with lipid synthesis is unclear. Here, we show that Faa1, an enzyme activating fatty acids, is directly recruited to Atg9 vesicles. We further show that Faa1 binds to negatively charged membranes. We define the membrane binding surface in Faa1 and show that membrane binding is required for its enzymatic activity. In cells, membrane binding by Faa1 is required for its recruitment to phagophores and promotes autophagosome biogenesis. Our results suggest a positive feedback loop coupling phagophore nucleation and expansion to lipid synthesis. SummaryBaumann, Achleitner, Tulli et al. dissect Faa1 function and recruitment during autophagy. They discover that Faa1 directly binds membranes via a positively charged surface. This is a prerequisite for Faa1s enzymatic activity sustaining autophagosome biogenesis.

biochemistry↗

bioRxiv2020

Multiple roles for the ESCRT machinery in maintaining plasma membrane homeostasis

The endosomal sorting complexes required for transport (ESCRT) execute evolutionary conserved membrane remodeling processes. Here we used budding yeast to explore how the ESCRT machinery contributes to plasma membrane (PM) homeostasis. In response to reduced membrane tension and inhibition of the target of rapamycin complex 2 (TORC2), ESCRT-III/Vps4 assemblies form at the PM and help to maintain membrane integrity. Conversely, the growth of ESCRT mutants strongly depends on TORC2-mediated homeostatic regulation of sphingolipid (SL) metabolism. This is caused by calcineurin phosphatase activity which causes Orm2 to accumulate at the endoplasmic reticulum (ER) in ESCRT mutants. Orm2 is a repressor of SL biosynthesis and its accumulation provokes increased membrane stress. This necessitates TORC2 signaling through its downstream kinase Ypk1 to control Orm2 protein levels and prevent a detrimental imbalance of SL metabolism. Our findings reveal new aspects of antagonistic calcineurin/TORC2 signaling for the regulation of SL biosynthesis and the maintenance of PM homeostasis, and suggest that the ESCRT machinery contributes directly and indirectly to these processes.

cell biology↗