title: Survival of mycobacteria depends on proteasome-mediated amino acid recycling under nutrient limitation.
abstract: Intracellular protein degradation is an essential process in all life domains. While in all eukaryotes regulated protein degradation involves ubiquitin tagging and the 26S-proteasome, bacterial prokaryotic ubiquitin-like protein (Pup) tagging and proteasomes are conserved only in species belonging to the phyla Actinobacteria and Nitrospira. In Mycobacterium tuberculosis, the Pup-proteasome system (PPS) is important for virulence, yet its physiological role in non-pathogenic species has remained an enigma. We now report, using Mycobacterium smegmatis as a model organism, that the PPS is essential for survival under starvation. Upon nitrogen limitation, PPS activity is induced, leading to accelerated tagging and degradation of many cytoplasmic proteins. We suggest a model in which the PPS functions to recycle amino acids under nitrogen starvation, thereby enabling the cell to maintain basal metabolic activities. We also find that the PPS auto-regulates its own activity via pupylation and degradation of its components in a manner that promotes the oscillatory expression of PPS components. As such, the destructive activity of the PPS is carefully balanced to maintain cellular functions during starvation.
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Yifat
authors.initials: Y
authors.lastname: Elharar
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Roth
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Inna
authors.initials: I
authors.lastname: Hermelin
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Moon
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Peretz
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Shenkerman
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Marina
authors.initials: M
authors.lastname: Vishkautzan
authors.affiliation: The Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Isam
authors.initials: I
authors.lastname: Khalaila
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel gure@bgu.ac.il.
authors.forename: Eyal
authors.initials: E
authors.lastname: Gur
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002244:Carbon / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006706:Homeostasis; D009154:Mutation; D020102:Mycobacterium smegmatis / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D009584:Nitrogen / Q000378:metabolism; D009876:Operon; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D002244:Carbon; D000255:Adenosine Triphosphate; D046988:Proteasome Endopeptidase Complex; D009584:Nitrogen
keywords: mycobacteria; nitrogen limitation; proteasome; proteolysis; pupylation