junior research group leader
Tel.: +49 228 - 73 - 6 27 08
Peroxisomes are highly dynamic organelles present in almost every eukaryotic cell. Once considered ancestral remnants and redundant in their function to mitochondria, their importance is highlighted by the human disease class Peroxisomal Biogenesis Disorders (PBD): rare, fatal diseases caused by mutation in peroxisome assembly factors. Recent research has extended the role of peroxisomes and links them to lipid droplet formation and innate immunity.
Peroxisomal metabolism is tightly linked to mitochondrial metabolism: fatty acids of chain lengths longer than C20 (very long chain fatty acids, VLCFA) have to be shortened by the peroxisomal oxidation machinery, before they can enter the mitochondrion for energy gain. Upon peroxisome dysfunction, VLCFA accumulate. Peroxisomes and mitochondria also share their fusion and fission machinery, and mitochondria play an important role in peroxisome de novo biogenesis.
We found that in a Drosophila PBD model, a mutant lacking the peroxisome biogenesis factor Pex19, hyperactivation of lipolysis and mitochondrial β-oxidation leads to free fatty acid (FFA) accumulation and mitochondrial swelling. The lipid profile, apart from the expected enrichment of VLCFA, shows a reduction of lipids with medium chain length (MCFA), which causes energy problems in Pex19 mutants. Furthermore, we found that, while VLCFA accumulate upon peroxisome loss, medium-chain fatty acids (MCFA) are reduced. MCFA directly fuel the mitochondrial β-oxidation machinery for energy gain. We found that a dietary rescue with 5% of oils which contain high concentrations of lauric (C12:0) and myristic (C14:0) acid can compensate for the loss of a whole organelle.
My current research focuses on the question how peroxisomes influence mitochondrial metabolism such that upon peroxisome loss, mitochondria increase the consumption of MCFA. Also, I am interested in how peroxisomes link FFA to diabetes. I am studying the role of peroxisomes in an organelle network required for sensing of nutrients. I am collaborating with Prof. Di Cara from Dalhousie University in Halifax on the impact of peroxisome dysfunction on neurodegeneration.
My research is funded by the German Research Association and the New Frontiers in Research Fund.
Di Cara F, Bülow MH, Simmonds A, Rachubinski R. Dysfunctional peroxisomes compromise gut structure and host defense by increased cell death and Tor-dependent autophagy. Mol Biol Cell. 2018 Nov 1;29(22):2766-2783.
Sellin J, Wingen C, Gosejacob D, Senyilmaz D, Hänschke L, Büttner S, Meyer M, Bano D, Nicotera P, Teleman AA and Bülow MH. Dietary rescue of lipotoxicity-induced mitochondrial damage in Peroxin19 mutants. PLoS Biol. 2018 Jun 19;16(6):e2004893.
Bülow MH, Wingen C, Senyilmaz D, Gosejacob D, Sociale M, Bauer R, Teleman AA, Hoch M, Sellin S. Unbalanced lipolysis resulting in lipotoxicity provokes mitochondrial damage in peroxisome-deficient Pex19 mutants. Mol Biol Cell. 2018 Feb 15;29(4):396-407.