Quality control of biological membranes by dedicated sensors

Datum

27.02.2020

Zeit

11:00 - 12:00

Sprecher

Robert Ernst

Zugehörigkeit

Saarland University, Homburg, Germany

Sprache

en

Hauptthema

Biologie

Host

Alf Honigmann

Beschreibung

Lipids and proteins shape the physicochemical properties of cellular membranes as a collective, thereby affecting membrane protein function and contributing to organelle identity. Eukaryotic cells face the challenge of maintaining the complex composition of several coexisting organelles during stress, adaptation, and cellular development. The molecular mechanisms underlying the homeostasis of subcellular membranes and their adaptation during stress are only starting to emerge. We have studied three membrane property sensors of the endoplasmic reticulum (ER), namely OPI1, MGA2, and IRE1, each controlling transcriptional programs impacting on the lipid metabolic network. OPI1 coordinates the production of membrane and storage lipids (Hofbauer et al., 2018), MGA2 regulates the production of unsaturated fatty acids required for membrane biogenesis (Covino et al., 2016), and IRE1 controls the unfolded protein response (UPR) to adjust the abundance of ER membranes and its protein folding capacity (Halbleib et al., 2017). Although these three machineries use remarkably distinct sensing mechanisms, they are functionally connected via the ER membrane and cooperate to maintain membrane homeostasis. We are currently studying their crosstalk and collective functions coordinating the composition and properties of the ER. We are in the process of studying how ER stress propagates throughout the cell. To this end, we are developing tools to biochemically isolate organelles from stressed and unstressed cells. Based on our findings, we propose that the unfolded protein response mediated by IRE1 can sense the protein-to-lipid ratio in the ER membrane to warrant a balanced production of membrane proteins and lipids.

Letztmalig verändert: 28.02.2020, 00:08:39