Unraveling the role of the Target of Rapamycin signaling in sphingolipid metabolism |
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| Institution: | 1. Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal;2. IBMC, Instituto de Biologia Molecular e Celular, Porto, Portugal;3. ICBAS, Instituto de Ciências Biomédicas Abel Salazar, Departamento de Biologia Molecular, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal;1. Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794-5215, USA;2. Department of Chemical and Biomolecular Engineering, Ohio University, Athens, OH 45701, USA;1. iMed.ULisboa - Research Institute for Medicines, Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, Lisboa 1649-003, Portugal;2. Centro de Química e Bioquímica (CQB) e Centro de Química Estrutural (CQE), Faculdade de Ciências, Universidade de Lisboa, Ed. C8, Campo Grande, Lisboa 1749-016, Portugal;3. Sir Martin Evans Building, School of Biosciences, Cardiff University, Cardiff, UK;4. Centro de Química-Física Molecular - Institute of Nanoscience and Nanotechnology (CQFM-IN), IBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal;5. Institute for Clinical Chemistry, University Hospital Zurich, Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Switzerland |
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| Abstract: | Sphingolipids are important bioactive molecules that regulate basic aspects of cellular metabolism and physiology, including cell growth, adhesion, migration, senescence, apoptosis, endocytosis, and autophagy in yeast and higher eukaryotes. Since they have the ability to modulate the activation of several proteins and signaling pathways, variations in the relative levels of different sphingolipid species result in important changes in overall cellular functions and fate.Sphingolipid metabolism and their route of synthesis are highly conserved from yeast to mammalian cells. Studies using the budding yeast Saccharomyces cerevisiae have served in many ways to foster our understanding of sphingolipid dynamics and their role in the regulation of cellular processes. In the past decade, studies in S. cerevisiae have unraveled a functional association between the Target of Rapamycin (TOR) pathway and sphingolipids, showing that both TOR Complex 1 (TORC1) and TOR Complex 2 (TORC2) branches control temporal and spatial aspects of sphingolipid metabolism in response to physiological and environmental cues. In this review, we report recent findings in this emerging and exciting link between the TOR pathway and sphingolipids and implications in human health and disease. |
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