Autophagy - Autophagy
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EMBO Molecular Medicine cross-journal focus Autophagy - Autophagy EDITORS Andrea Leibfried Editor andrea.leibfried@embo.org | T + Andrea worked with Jan Lohmann on stem cell maintenance in the plant Arabidopsis before moving to the eld of trafcking. In she obtained her PhD from the Université Pierre et Marie Curie in Paris, for which she studied DE-Cadherin trafcking in Drosophila with Yohanns Bellaiche at the Curie Institute. She then went to Anne Ephrussi’s lab at the EMBL in Heidelberg to work on oocyte polarity and mRNA trafcking in Drosophila. Andrea joined The EMBO Journal in . Nonia Pariente Senior Editor pariente@embo.org | T + Nonia joined EMBO Reports in August . She studied biochemistry and molecular biology in Madrid’s Autónoma University, where she also gained her PhD on the generation of new antiviral strategies against RNA viruses. She did a four-year post-doc at UCLA focusing on the development of new strategies for gene therapy. Céline Carret Editor c.carret@embomolmed.org | T + Céline Carret completed her PhD at the University of Montpellier, France, characterising host immunodominant antigens to ght babesiosis, a parasitic disease caused by a unicellular EMBO Apicomplexan parasite closely related to the malaria agent Plasmodium. She further developed Molecular her post-doctoral career on malaria working at the Wellcome Trust Sanger Institute in Cambridge, Medicine UK and Instituto de Medicina Molecular in Lisbon, Portugal. Céline joined EMBO Molecular Medicine as a Scientic Editor in March . Maria Polychronidou Editor maria.polychronidou@embo.org | T + Maria received her PhD from the University of Heidelberg, where she studied the role of nuclear membrane proteins in development and aging. During her post-doctoral work, she focused on the analysis of tissue-specic regulatory functions of Hox transcription factors using a combination of computational and genome-wide methods. emboj.embopress.org | embor.embopress.org | embomolmed.embopress.org | msb.embopress.org full articles The EMBO Journal Article Induction of autophagy supports the bioenergetic demands of quiescent muscle stem cell activation. Tang AH, Rando TA. DOI:10.15252/embj.201488278 | Published 14.10.2014 EMBO Reports Review Getting ready for building: signaling and autophagosome biogenesis. Abada A, Elazar Z. DOI:10.15252/embr.201439076 | Published 15.07.2014 Article PI3P phosphatase activity is required for autophagosome maturation and autolysosome formation. Wu Y, Cheng S, Zhao H, Zou W, Yoshina S, Mitani S, Zhang H, Wang H. DOI:10.15252/embr.201438618| Published 14.08.2014 EMBO Molecular Medicine Articles Lysosomal dysfunction and impaired autophagy underlie the pathogenesis of amyloidogenic light chain-mediated cardiotoxicity. Guan J, Mishra S, Qiu Y, Shi J, Trudeau K, Las G, Liesa M, Shirihai OS, Connors LH, Seldin DC, Falk RH, MacRae CA, Liao R. DOI:10.15252/emmm.201404190 | Published 15.10.2014 Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB. Polito VA, Li H, Martini-Stoica H, Wang B, Yang L, Xu Y, Swartzlander DB, Palmieri M, di Ronza A, Lee VMY, Sardiello M, Ballabio A, Zheng H. DOI:10.15252/emmm.201303671 | Published 28.07.2014 For further reading please see inside back cover Article Induction of autophagy supports the bioenergetic demands of quiescent muscle stem cell activation Ann H Tang1,2 & Thomas A Rando1,2,3,*,† Abstract autophagy can protect cells against nutrient stress (Mizushima & Komatsu, 2011). Nitrogen-starved yeast, for example, induce auto- The exit of a stem cell out of quiescence into an activated state is phagy to produce amino acids to maintain viability (Onodera & characterized by major metabolic changes associated with Ohsumi, 2005). Similarly, lymphocytes subjected to growth factor increased biosynthesis of proteins and macromolecules. The regu- deprivation that prevents nutrient uptake activate autophagy to lation of this transition is poorly understood. Using muscle stem survive (Lum et al, 2005). Autophagy can also safeguard against cells, or satellite cells (SCs), we found that autophagy, which nutrient deprivation at the organismal level, as studies have shown catabolizes intracellular contents to maintain proteostasis and to that mice rely on autophagy to survive the neonatal starvation produce energy during nutrient deprivation, was induced during period (Kuma et al, 2004; Komatsu et al, 2005). SC activation. Inhibition of autophagy suppressed the increase in More recent studies have demonstrated that autophagy also serves ATP levels and delayed SC activation, both of which could be as an adaptive response to many other stressors including intense partially rescued by exogenous pyruvate as an energy source, exercise, ER stress, infection, hypoxia, and oxidative stress (He & suggesting that autophagy may provide nutrients necessary to Klionsky, 2009; Kroemer et al, 2010; He et al, 2012). For example, meet bioenergetic demands during this critical transition from autophagy responds to oxidative stress by removing damaged quiescence to activation. We found that SIRT1, a known nutrient mitochondria (Wen et al, 2013). Furthermore, autophagy can also sensor, regulates autophagic flux in SC progeny. A deficiency of eliminate intracellular pathogens, such as viruses and bacteria (Yano SIRT1 led to a delay in SC activation that could also be partially & Kurata, 2011). Interestingly, autophagy may also facilitate the rescued by exogenous pyruvate. These studies suggest that auto- immune response to infection, as resting T cells in which autophagy is phagy, regulated by SIRT1, may play an important role during SC inhibited cannot activate (Hubbard et al, 2010). Blocking autophagy activation to meet the high bioenergetic demands of the activation would therefore hinder the ability of a cell to respond to stress. process. Stem cells depend on intact autophagic machinery for the mainte- nance of states, characteristics, and processes that underlie stem cell Keywords activation; autophagy; quiescence; satellite cell; SIRT1 functions. When autophagy is inhibited, defects in quiescence, differ- Subject Categories Autophagy & Cell Death; Metabolism; Stem Cells entiation, and self-renewal have been reported (Guan et al, 2013; DOI 10.15252/embj.201488278 | Received 19 February 2014 | Revised 29 Phadwal et al, 2013). It has been proposed that long-lived stem cells August 2014 | Accepted 1 September 2014 that rarely divide rely on autophagy to remove damaged proteins and organelles for the maintenance of quiescence (Guan et al, 2013). This is supported by findings that HSCs that accumulate mitochon- dria and reactive oxygen species fail to maintain quiescence when Introduction blocked for autophagy (Liu et al, 2010; Mortensen et al, 2011). Addi- tionally, autophagy can selectively dispose of proteins and organelles Macroautophagy, hereafter referred to as autophagy, is a homeo- that can inhibit normal differentiation and self-renewal of stem cells static process with dual functions as a cellular quality control mech- (Mortensen et al, 2010, 2011; Mizushima & Komatsu, 2011). anism and a recycling system (Mizushima & Komatsu, 2011; Singh While the autophagic removal of damaged or extraneous cellular & Cuervo, 2011). Double-membraned structures engulf cytoplasmic components has been shown to be necessary for the maintenance components into vesicles called autophagosomes that later fuse with and function of stem cells, the contribution of autophagy to the lysosomes to break down their contents from which amino acids metabolic needs of stem cells has been less well studied. Pathways and other degradation products may be recycled for protein synthe- and molecules that sense and regulate cellular energy status, sis or for the tricarboxylic acid (TCA) cycle to generate energy however, have been well documented to influence stem cell func- (Ravikumar et al, 2010; Yang & Klionsky, 2010). In this way, tion (Rafalski & Brunet, 2011; Folmes et al, 2012). Manipulations of 1 Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA, USA 2 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA 3 Neurology Service and Rehabilitation Research and Developmental Center of Excellence, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA *Corresponding author. Tel: +1 650 849 1999; E-mail: rando@stanford.edu †This article has been contributed to by US Government employees and their work is in the public domain in the USA ª 2014 The Authors The EMBO Journal 1 The EMBO Journal Autophagy in satellite cell activation Ann H Tang & Thomas A Rando Ann H Tang & Thomas A Rando Autophagy in satellite cell activation The EMBO Journal the mTOR pathway, for example, have been reported to perturb SCs results in a phenotype similar to that observed when autophagy A pluripotency, proliferation, differentiation, and self-renewal of stem is inhibited. Together, these data suggest a model in which the cells (Murakami et al, 2004; Chen et al, 2008; Sampath et al, 2008; metabolic demands of SC activation are sensed by SIRT1 which in Zhou et al, 2009; Easley et al, 2010). Since downstream targets of turn activates the autophagic machinery in order to generate nutri- these metabolic pathways include components of the autophagic ents that are essential for the generation of ATP to support that machinery, the significance of the bioenergetic contributions from enormous increase in synthetic