title: Autophagy meets fused in sarcoma-positive stress granules.
abstract: Mutations in fused in sarcoma and/or translocated in liposarcoma (FUS, TLS or FUS) are linked to familial cases of amyotrophic lateral sclerosis (ALS). Mutant FUS selectively accumulates into discrete cytosolic structures known as stress granules under various stress conditions. In addition, mutant FUS expression can alter the dynamics and morphology of stress granules. Although the link between mutant FUS and stress granules is well established, the mechanisms modulating stress granule formation and disassembly in the context of ALS are poorly understood. In this issue of Neurobiology of Aging, Ryu et al. uncover the impact of autophagy on the potential toxicity of mutant FUS-positive stress granules. The authors provide evidence indicating that enhanced autophagy activity reduces the number of stress granules, which in the case of cells containing mutant FUS-positive stress granules, is neuroprotective. Overall, this study identifies an intersection between the proteostasis network and alterations in RNA metabolism in ALS through the dynamic assembly and disassembly of stress granules.
authors.affiliation: Neurounion Biomedical Foundation, CENPAR, Santiago, Chile; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile. Electronic address: soledad.matus@neurounion.com.
authors.forename: Soledad
authors.initials: S
authors.lastname: Matus
authors.affiliation: Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Daryl A
authors.initials: DA
authors.lastname: Bosco
authors.affiliation: Neurounion Biomedical Foundation, CENPAR, Santiago, Chile; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile; Program of Cellular and Molecular Biology, Center for Molecular Studies of the Cell, Institute of Biomedical Sciences, University of Chile, Santiago, Chile. Electronic address: chetz@med.uchile.cl.
authors.forename: Claudio
authors.initials: C
authors.lastname: Hetz
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D001343:Autophagy / Q000235:genetics* / Q000502:physiology*; D003594:Cytoplasmic Granules / Q000378:metabolism* / Q000473:pathology*; D015870:Gene Expression; D056726:Genetic Association Studies; D006801:Humans; D009154:Mutation; D012313:RNA / Q000378:metabolism; D034702:RNA-Binding Protein FUS / Q000235:genetics* / Q000378:metabolism
chemical_list: C000599550:FUS protein, human; D034702:RNA-Binding Protein FUS; D012313:RNA
keywords: ALS; Autophagy; FUS; Stress granules