Membrane Contact Sites
Eukaryotic cells are strongly compartmentalized to provide spatial separation for various processes of synthesis and degradation. Organelles can maintain conditions for processes as diverse as protein folding and modification, lipid biosynthesis, lipid storage, fatty acid oxidation and degradation of bulk material. To harmonize these processes, organelles form contact sites that serve the exchange of material and regulate their abundance and activity. Our lab studies organelle contact sites in tissue of the fruitfly Drosophila melanogaster. In particular, we want to understand how organelle communication shapes the morphology and function of neurons. We showed how loss of peroxisome function leads to dysregulation of mitochondrial fatty acid oxidation and induces systemic lipolysis (Bülow et al., 2018; Sellin et al., 2018), which leads to neurodegeneration. We are currently investigating the interactions of peroxisomes with other organelles in peptidergic neurons, such as insulin-producing cells. We also demonstrated that disturbed contact formation between the endoplasmic reticulum (ER) and mitochondria alters the formation of reactive oxygen species (ROS) in mitochondria and inhibits the activity of both dopaminergic neurons and of the heart (Paradis et al., 2022). Our aim is to understand how a subcellular process, namely organelle communication, impacts on the physiology of the organism, in health and disease.
Team
PD Dr. Margret Bülow
Nicole Kucharowski
Darla Patricia Dancourt Ramos
Thi Minh Nghi Nguyen
Torsten Bülow
Funding
Our research is funded by the German Research Foundation (DFG), grant numbers 535112684 and 417982926 (to MB)
Selected Publications
Carrera P, Odenthal J, Risse KS, Jung Y, Kuerschner L, Bülow MH. The CD36 scavenger receptor Bez regulates lipid redistribution from fat body to ovaries in Drosophila. Development. 2024 May 1;151(9):dev202551. doi: 10.1242/dev.202551.
Paradis M, Kucharowski N, Edwards Faret G, Maya Palacios SJ, Meyer C, Stümpges B, Jamitzky I, Kalinowski J, Thiele C, Bauer R, Paululat A, Sellin J, Bülow MH. The ER protein Creld regulates ER-mitochondria contact dynamics and respiratory complex 1 activity. Sci Adv. 2022 Jul 22;8(29):eabo0155. doi: 10.1126/sciadv.abo0155.
Hänschke L, Heier C, Maya Palacios SJ, Özek HE, Thiele C, Bauer R, Kühnlein RP, Bülow MH. Drosophila Lipase 3 Mediates the Metabolic Response to Starvation and Aging. Front Aging. 2022 Feb 14;3:800153. doi: 10.3389/fragi.2022.800153.
Sellin J, Fülle JB, Thiele C, Bauer R, Bülow MH. Free fatty acid determination as a tool for modeling metabolic diseases in Drosophila. J Insect Physiol. 2020 Oct;126:104090. doi: 10.1016/j.jinsphys.2020.104090.
Sellin J, Wingen C, Gosejacob D, Senyilmaz D, Hänschke L, Büttner S, Meyer K, Bano D, Nicotera P, Teleman AA, Bülow MH. Dietary rescue of lipotoxicity-induced mitochondrial damage in Peroxin19 mutants. PLoS Biol. 2018 Jun 19;16(6):e2004893. doi: 10.1371/journal.pbio.2004893.
Bülow MH, Wingen C, Senyilmaz D, Gosejacob D, Sociale M, Bauer R, Schulze H, Sandhoff K, Teleman AA, Hoch M, Sellin J. Unbalanced lipolysis results in lipotoxicity and mitochondrial damage in peroxisome-deficient Pex19 mutants. Mol Biol Cell. 2018 Feb 15;29(4):396-407. doi: 10.1091/mbc.E17-08-0535.