Liebscher 2017 MiPschool Obergurgl
Event: MiPschool Obergurgl 2017
LAMTOR2 is part of the LAMTOR complex anchored to late endosomal/lysosomal membranes. The LAMTOR complex is known to regulate mTORC1 signaling in an amino acid dependent manner and MAPK signaling. Both signaling pathways play a crucial role in cellular homeostasis. [1,2,3] Deletions of LAMTOR components are early embryonic-lethal in mice, but conditional knockouts allow the study of the complex. Microarray and proteomic studies in LAMTOR2 -/- mouse embryonic fibroblasts (MEF) and macrophages point to a regulation of lipid metabolism including lipid synthesis, uptake, transport and degradation. The aim is to study the role of the LAMTOR complex in adipose tissue homeostasis and lipid metabolism.
The AdipoqLAMTOR2 -/- mice show an accumulation of lipids e.g. triglycerides in the blood, brown adipose tissue (BAT) and liver in chow diet. Under fasting and refeeding conditions a defect in activating mTORC1 signaling in BAT of these mice was observed. Furthermore, a microarray analysis revealed a deregulation of mitochondrial genes in BAT. Electron microscopy and respiratory measurement revealed no changes in overall mitochondrial morphology and physiology. Although thermogenesis and mitochondrial genes are downregulated in BAT of AdipoqLAMTOR2 -/- mice, cold treatment reverses the phenotype observed in BAT and blood.
- (1)Liebscher G, (1)Lamberti G, (1)De Smet CH, (1)Hermann C, (2)Vujic N, (4)Schreiber R, (3)Doerrier C, (5)Demetz E, (5)Tanchevski I, (2)Leopold C, (6)Moustafa T, (4)Zechner R, (3)Gnaiger E, (2)Kratky D, (1)Huber LA
- Div Cell Biol, Biocenter, Medical Univ Innsbruck
- Inst Molecular Biol Biochem, Medical Univ Graz
- Oroboros Instruments, Innsbruck
- Dept General Transplant Surgery, D. Swarovski Research Lab, Medical Univ Innsbruck
- Inst Molecular Biosciences, Univ Graz
- Dept Internal Medicine VI, Med Univ Innsbruck
- Lab Experimental Molecular Hepatol, Div Gastroenterol Hepatol, Dept Internal Medicine, Med Univ Graz
- Austria.- [email protected]
- Wunderlich W, Fialka I, Teis D, Alpi A, Pfeifer A, Parton RG, Lottspeich F, Huber LA (2001) A novel 14-kilodalton protein interacts with the mitogen‐activated protein kinase scaffold mp1 on a late endosomal/lysosomal compartment. J Cell Biol 152:765‐76.
- Teis D1, Taub N, Kurzbauer R, Hilber D, de Araujo ME, Erlacher M, Offterdinger M, Villunger A, Geley S, Bohn G, Klein C, Hess MW, Huber LA (2006) p14-MP1-MEK1 signaling regulates endosomal traffic and cellular proliferation during tissue homeostasis. J Cell Biol 175:861-8.
- Sancak Y, Bar-Peled L, Zoncu R, Markhard AL, Nada S, Sabatini DM (2010) Ragulator‐Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 141:290-303.
Labels: MiParea: Respiration, mtDNA;mt-genetics, Genetic knockout;overexpression
Organism: Mouse Tissue;cell: Fat
HRR: Oxygraph-2k Event: D2, Oral