The importance of proteostasis is becoming increasingly apparent as disrupted proteostasis and dysregulation of proteostasis-associated networks has been linked with aging and many age-associated diseases such as Alzheimer’s, Parkinson’s and Huntington’s disorders. In recognition of the importance of this subject, PLOS ONE, alongside PLOS Biology, launched a Call for Papers on the topic of Autophagy and Proteostasis earlier this year. We welcomed a range of submissions that provided insight into the molecular and cellular machinery, and mechanisms that regulate autophagy and the crosstalk of this process with other protein quality control pathways to ensure proteostasis. These studies also underline the importance of all these cellular pathways in pathophysiological conditions and aging. The Guest Editors are Sharon Tooze (Francis Crick Institute, United Kingdom), Fulvio Reggiori (University Medical Centre Groningen, The Netherlands) and Thorsten Hoppe (Institute for Genetics and CECAD Center for Aging Research, University of Cologne, Germany).
We are happy to launch this Collection today, which includes five studies published in PLOS ONE that highlight the relevance of autophagy and other pathways such as the ubiquitin proteasome-system in maintaining protein homeostasis. In human cells, Ferreira et al. showed that when the STUB1/CHIP ubiquitin ligase is inactivated, cells increase secretion of extracellular vesicles (EVs) enriched in ubiquitylated or stabilized proteins, suggesting that cells use these EVs to dispose of proteotoxic material. Studying another E3 ubiquitin ligase, Si and colleagues investigate the mechanism for Pink1- and Parkin-mediated mitophagy in indirect flight muscles in Drosophila melanogaster, and showed that Pink1/Parkin are crucial for muscle function in aged muscles in an Atg1-dependent manner. Autophagy also plays crucial roles in the fungus Aspergillus niger and Kaur and Punekar revealed that acidogenic growth appears to mimic a nutrient deficient condition, and acidogenic growth and metabolism are compromised in Δatg1 and Δatg8 strains of A. niger.
In addition, two papers in the Collection showcase research investigating proteostasis dysfunction in disease states, and potential ways to modulate autophagy for therapeutic uses. Aviazidis et al. study proteostasis network dysfunction caused by unbalanced karyotypes using human Down’s syndrome fibroblasts, showing that decreased abundance of SNARE family members STX17 and VAMP8 maybe responsible for reducing autophagic flux by impairing autophagosome-lysosome fusion. Bhaskar et al. identify lipoarabinomannan (LAM), a crucial lipid component of the Mycobacterium indicius pranii cell-wall, as an inducer of autophagy that leads to the enhancement of co-localization between Mycobacteriaum tuberculosis and phago-lysosomes, and increased clearance of this bacterium in macrophages.
Papers will continue to be added to the Collection as they are published. Stay tuned for new articles and additional insights on this important topic.
About the Guest Editors
Fulvio Reggiori is a Professor and Section Head of Molecular Cell Biology at the Department of Biomedical Sciences of Cells and Systems of the University Medical Centre Groningen, The Netherlands. Fulvio obtained in his PhD in Biochemistry from the University of Fribourg, Switzerland, in the laboratory of Professor Andreas Conzelmann. Subsequently, he moved to the MRC Laboratory in Molecular Biology in Cambridge to join the laboratory of Dr. Hugh Pelham, UK in 1998. In 2001, Fulvio moved to the University of Michigan in Ann Arbor, USA to the laboratory of Professor Daniel Klionsky, where he started working on different aspects of the molecular mechanisms of autophagy in yeast. In 2005 he was appointed as an Assistant Professor at the Department of Cell Biology of the University Medical Center Utrecht, The Netherlands before becoming an Associate Professor in 2011. Fulvio moved his lab in 2015, to the Department of Department of Biomedical Sciences of Cells and Systems of the University Medical Center Groningen where he became Professor. His research continues to investigate the molecular mechanisms of autophagy using Saccharomyces cerevisiae as a model organism as well as understanding the interaction between autophagy and pathogens, in particular viruses.
Sharon Tooze is a Senior Group Leader at the Francis Crick Institute, London, UK. She has a long-standing interest in understanding organelle biogenesis using molecular cell biology approaches. Sharon received her PhD and undertook a postdoctoral research position in Wieland Huttner’s lab at the European Molecular Biology Laboratory (EMBL). She established a lab at Imperial Cancer Research Fund, UK which later became known as the Cancer Research UK London Research Institute. In 2015 she moved her lab to the Francis Crick Institute where her research continues to focus on autophagy. Her current interests are focused on expanding our knowledge of the core autophagy proteins in mammalian cells at the molecular level, in particular the autophagy proteins which initiate the formation of the autophagosome.
Thorsten Hoppe is a Professor at the Institute for Genetics and the Center for Aging Research (CECAD) at the University of Cologne, Germany. He received his PhD from the University of Heidelberg working in the lab of Stefan Jentsch at the Center for Molecular Biology in Heidelberg (ZMBH) and the Max Planck Institute of Biochemistry in Martinsried. He undertook is postdoctoral work in the Department of Molecular Neurogenetics in the group of Ralf Baumeister at the LM-University of Munich before setting up his own group in 2003 at the Centre for Molecular Neurobiologie at the University of Hamburg (ZMNH). In 2008 he moved his lab to the Institute for Genetics and was Acting Director from 2011 to 2013. His research focuses on understanding the role proteostasis plays in aging and age-associated diseases.