• Aggrephagy: Selective Disposal of Protein Aggregates by Macroautophagy 

      Lamark, Trond; Johansen, Terje (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)
      Protein aggregation is a continuous process in our cells. Some proteins aggregate in a regulated manner required for different vital functional processes in the cells whereas other protein aggregates result from misfolding caused by various stressors. The decision to form an aggregate is largely made by chaperones and chaperone-assisted proteins. Proteins that are damaged beyond repair are degraded ...
    • ATG8 Family Proteins Act as Scaffolds for Assembly of the ULK Complex SEQUENCE REQUIREMENTS FOR LC3-INTERACTING REGION (LIR) MOTIFS 

      Alemu, Endalkachew Ashenafi; Lamark, Trond; Torgersen, Knut Martin; Birgisdottir, Åsa birna; Larsen, Kenneth Bowitz; Jain, Ashish; Olsvik, Hallvard Lauritz; Øvervatn, Aud Karin; Kirkin, Vladimir; Johansen, Terje (Journal article; Tidsskriftartikkel; Peer reviewed, 2012-10-05)
      Autophagy is a lysosome-dependent degradation system conserved among eukaryotes. The mammalian Atg1 homologues, Unc-51 like kinase (ULK) 1 and 2, are multifunctional proteins with roles in autophagy, neurite outgrowth, and vesicle transport. The mammalian ULK complex involved in autophagy consists of ULK1, ULK2, ATG13, FIP200, and ATG101. We have used pulldown and peptide array overlay assays to ...
    • Atg8 family proteins, LIR/AIM motifs and other interaction modes 

      Rogov, Vladimir V.; Nezis, Ioannis P.; Tsapras, P; Zhang, Hong; Dagdas, Yasin; Noda, Nobuo N; Nakatogawa, Hitoshi; Wirth, Martina; Mouilleron, Stephane; McEwan, David G.; Behrends, Christian; Deretic, Vojo P.; Elazar, Zvulun; Tooze, Sharon A.; Dikic, Ivan; Lamark, Trond; Johansen, Terje (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-03-19)
      The Atg8 family of ubiquitin-like proteins play pivotal roles in autophagy and other processes involving vesicle fusion and transport where the lysosome/vacuole is the end station. Nuclear roles of Atg8 proteins are also emerging. Here, we review the structural and functional features of Atg8 family proteins and their protein-protein interaction modes in model organisms such as yeast, Arabidopsis, ...
    • CALCOCO1 acts with VAMP ‐associated proteins to mediate ER ‐phagy 

      Nthiga, Thaddaeus Mutugi; Shrestha, Birendra Kumar; Sjøttem, Eva; Bruun, Jack-Ansgar; Larsen, Kenneth Bowitz; Bhujabal, Zambarlal; Lamark, Trond; Johansen, Terje (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-06-11)
      The endoplasmic reticulum (ER) plays important roles in protein synthesis and folding, and calcium storage. The volume of the ER and expression of its resident proteins are increased in response to nutrient stress. ER‐phagy, a selective form of autophagy, is involved in the degradation of the excess components of the ER to restore homeostasis. Six ER‐resident proteins have been identified as ER‐phagy ...
    • CALCOCO1 is a soluble reticulophagy receptor 

      Mutugi Nthiga, Thaddaeu; Shrestha, Birendra Kumar; Lamark, Trond; Johansen, Terje (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-07-25)
      The endoplasmic reticulum (ER) is the largest membrane-bound organelle in eukaryotic cells and plays critical roles in diverse processes in metabolism, signaling and intracellular organization. In response to stress stimuli such as nutrient deprivation, accumulation of misfolded proteins or exposure to chemicals, the ER increases in size through upregulated synthesis of its components to counteract ...
    • DOR/Tp53inp2 and Tp53inp1 Constitute a Metazoan Gene Family Encoding Dual Regulators of Autophagy and Transcription 

      Sancho, Ana; Duran, Jordi; Garcia-Espana, Antonio; Mauvezin, Caroline; Alemu, Endalkachew Ashenafi; Lamark, Trond; Macias, Maria J.; DeSalle, Rob; Royo, Miriam; Sala, David; Chicote, Javier U.; Palacin, Manuel; Johansen, Terje; Zorzano, Antonio (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)
      Human DOR/TP53INP2 displays a unique bifunctional role as a modulator of autophagy and gene transcription. However, the domains or regions of DOR that participate in those functions have not been identified. Here we have performed structure/function analyses of DOR guided by identification of conserved regions in the DOR gene family by phylogenetic reconstructions. We show that DOR is present in ...
    • Dynamic subcellular localization of the mono-ADP-ribosyltransferase ARTD10 and interaction with the ubiquitin receptor p62 

      Kleine, Henning; Herrmann, Andreas; Lamark, Trond; Forst, Alexandra H.; Verheugd, Patricia; Lüscher-Firzlaff, Juliane; Lippok, Barbara; Feijs, Karla LH; Herzog, Nicolas; Kremmer, Elisabeth; Johansen, Terje; Müller-Newen, Gerhard; Lüscher, Bernhard (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)
      ADP-ribosylation is a posttranslational modification catalyzed in cells by ADP-ribosyltransferases (ARTD or PARP enzymes). The ARTD family consists of 17 members. Some ARTDs modify their substrates by adding ADP-ribose in an iterative process, thereby synthesizing ADP-ribose polymers, the best-studied example being ARTD1/PARP1. Other ARTDs appear to mono-ADP-ribosylate their substrates and are unable ...
    • The FMRpolyGlycine protein mediates aggregate formation and toxicity independent of the CGG mRNA hairpin in a cellular model for FXTAS 

      Hoem, Gry; Larsen, Kenneth Bowitz; Øvervatn, Aud Karin; Brech, Andreas; Lamark, Trond; Sjøttem, Eva; Johansen, Terje (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-03-28)
      Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a CGG-repeat expansion in the 5′ UTR of the FMR1 gene on the X-chromosome. Both elevated levels of the expanded FMR1 mRNA and aberrant expression of a polyglycine protein (FMRpolyG) from the CGG-repeat region are hypothesized to trigger the pathogenesis of FXTAS. While increased expression of FMRpolyG leads ...
    • FYCO1 contains a C-terminally extended, LC3A/B-preferring LC3-interacting region (LIR) motif required for efficient maturation of autophagosomes during basal autophagy 

      Olsvik, Hallvard Lauritz; Lamark, Trond; Takagi, Kenji; Larsen, Kenneth Bowitz; Evjen, gry; Øvervatn, Aud Karin; Mizushima, Tsunehiro; Johansen, Terje (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-10-14)
      FYCO1 (FYVE and coiled-coil protein 1) is a transport adaptor that binds to phosphatidylinositol 3-phosphate, to Rab7, and to LC3 (microtubule-associated protein 1 light chain 3) to mediate transport of late endosomes and autophagosomes along microtubules in the plus end direction. We have previously shown that FYCO1 binds to LC3B via a 19-amino acid sequence containing a putative core LC3-interacting ...
    • The inflammation repressor TNIP1/ABIN-1 is degraded by autophagy following TBK1 phosphorylation of its LIR 

      Rasmussen, Nikoline Lander; Zhou, Jianwen; Olsvik, Hallvard Lauritz; Kaeser-Pebernard, Stéphanie; Lamark, Trond; Dengjel, Joern; Johansen, Terje (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-03-09)
      The inflammatory repressor TNIP1/ABIN-1 is important for keeping in check inflammatory and cell-death pathways to avoid potentially dangerous sustained activation of these pathways. We have now found that TNIP1 is rapidly degraded by selective macroautophagy/autophagy early (0–4 h) after activation of TLR3 by poly(I:C)-treatment to allow expression of pro-inflammatory genes and proteins. A few hours ...
    • Mechanisms of Selective Autophagy 

      Lamark, Trond; Johansen, Terje (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-06-21)
      Selective autophagy is the lysosomal degradation of specific intracellular components sequestered into autophagosomes, late endosomes, or lysosomes through the activity of selective autophagy receptors (SARs). SARs interact with autophagy-related (ATG)8 family proteins via sequence motifs called LC3-interacting region (LIR) motifs in vertebrates and Atg8-interacting motifs (AIMs) in yeast and plants. ...
    • Members of the autophagy class III phosphatidylinositol 3-kinase complex I interact with GABARAP and GABARAPL1 via LIR motifs 

      Birgisdottir, Åsa Birna; Mouilleron, Stephane; Bhujabal, Zambarlal; Wirth, Martina; Sjøttem, Eva; Evjen, Gry; Zhang, Wenxin; Lee, Rebecca; O'Reilly, Nicola; Tooze, Sharon A; Lamark, Trond; Johansen, Terje (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-03-04)
      Autophagosome formation depends on a carefully orchestrated interplay between membrane-associated protein complexes. Initiation of macroautophagy/autophagy is mediated by the ULK1 (unc-51 like autophagy activating kinase 1) protein kinase complex and the autophagy-specific class III phosphatidylinositol 3-kinase complex I (PtdIns3K-C1). The latter contains PIK3C3/VPS34, PIK3R4/VPS15, BECN1/Beclin 1 ...
    • NBR1: The archetypal selective autophagy receptor 

      Rasmussen, Nikoline Lander; Kournoutis, Athanasios; Lamark, Trond; Johansen, Terje (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-10-18)
      NBR1 was discovered as an autophagy receptor not long after the first described vertebrate autophagy receptor p62/SQSTM1. Since then, p62 has currently been mentioned in >10,000 papers on PubMed, while NBR1 is mentioned in <350 papers. Nonetheless, evolutionary analysis reveals that NBR1, and likely also selective autophagy, was present already in the last eukaryotic common ancestor (LECA), while ...
    • NIMA-related kinase 9–mediated phosphorylation of the microtubule-associated LC3B protein at Thr-50 suppresses selective autophagy of p62/sequestosome 1 

      Shrestha, Birendra Kumar; Rasmussen, Mads Skytte; Abudu, Yakubu Princely; Bruun, Jack-Ansgar; Larsen, Kenneth Bowitz; Alemu, Endalkachew Ashenafi; Sjøttem, Eva; Lamark, Trond; Johansen, Terje (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-12-19)
      Human ATG8 family proteins (ATG8s) are active in all steps of the macroautophagy pathway, and their lipidation is essential for autophagosome formation. Lipidated ATG8s anchored to the outer surface of the phagophore serve as scaffolds for binding of other core autophagy proteins and various effector proteins involved in trafficking or fusion events, whereas those at the inner surface are needed for ...
    • NIPSNAP1 and NIPSNAP2 Act as “Eat Me” Signals for Mitophagy 

      Abudu, Yakubu Princely; Pankiv, Serhiy; Mathai, Benan John; Lystad, Alf Håkon; Bindesbøll, Christian; Brenne, Hanne Britt; Ng, Matthew Yoke Wui; Thiede, Bernd; Yamamoto, Ai; Nthiga, Thaddaeus Mutugi; Lamark, Trond; Esguerra, Camila Vicencio; Johansen, Terje; Simonsen, Anne (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-04-11)
      The clearance of damaged or dysfunctional mitochondria by selective autophagy (mitophagy) is important for cellular homeostasis and prevention of disease. Our understanding of the mitochondrial signals that trigger their recognition and targeting by mitophagy is limited. Here, we show that the mitochondrial matrix proteins 4-Nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog ...
    • P62/sequestosome-1, autophagy-related gene 8, and autophagy in Drosophila are regulated by nuclear factor erythroid 2-related factor 2(NRF2), independent of transcription factor TFEB 

      Jain, Ashish; Rusten, Tor Erik; Katheder, Nadja Sandra; Elvenes, Julianne; Bruun, Jack-Ansgar; Sjøttem, Eva; Lamark, Trond; Johansen, Terje (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-04-30)
      The selective autophagy receptor p62/sequestosome 1 (SQSTM1) interacts directly with LC3 and is involved in oxidative stress signaling in two ways in mammals. First, p62 is transcriptionally induced upon oxidative stress by the NF-E2-related factor 2 (NRF2) by direct binding to an antioxidant response element in the p62 promoter. Second, p62 accumulation, occurring when autophagy is impaired, leads ...
    • Regulation of Golgi turnover by CALCOCO1-mediated selective autophagy 

      Nthiga, Thaddaeus Mutugi; Shrestha, Birendra Kumar; Bruun, Jack-Ansgar; Larsen, Kenneth Bowitz; Lamark, Trond; Johansen, Terje (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-04-19)
      The Golgi complex is essential for the processing, sorting, and trafficking of newly synthesized proteins and lipids. Golgi turnover is regulated to meet different cellular physiological demands. The role of autophagy in the turnover of Golgi, however, has not been clarified. Here we show that CALCOCO1 binds the Golgi-resident palmitoyltransferase ZDHHC17 to facilitate Golgi degradation by autophagy ...
    • SAMM50 acts with p62 in piecemeal basal- and OXPHOS-induced mitophagy of SAM and MICOS components 

      Abudu, Yakubu Princely; Shrestha, Birendra Kumar; Zhang, Wenxin; Palara, Anthimi; Brenne, Hanne Britt; Larsen, Kenneth Bowitz; Wolfson, Deanna; Dumitriu, Gianina; Øie, Cristina Ionica; Ahluwalia, Balpreet Singh; Levy, Gahl; Behrends, Christian; Tooze, Sharon A; Mouilleron, Stephane; Lamark, Trond; Johansen, Terje (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-05-26)
      Mitophagy is the degradation of surplus or damaged mitochondria by autophagy. In addition to programmed and stress-induced mitophagy, basal mitophagy processes exert organelle quality control. Here, we show that the sorting and assembly machinery (SAM) complex protein SAMM50 interacts directly with ATG8 family proteins and p62/SQSTM1 to act as a receptor for a basal mitophagy of components of the ...
    • SAMM50 is a receptor for basal piecemeal mitophagy and acts with SQSTM1/p62 in OXPHOS-induced mitophagy 

      Abudu, Yakubu Princely; Mouilleron, Stephane; Tooze, Sharon A; Lamark, Trond; Johansen, Terje (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-07-18)
      Mitophagy, the clearance of surplus or damaged mitochondria or mitochondrial parts by autophagy, is important for maintenance of cellular homeostasis. Whereas knowledge on programmed and stress-induced mitophagy is increasing, much less is known about mechanisms of basal mitophagy. Recently, we identified SAMM50 (SAMM50 sorting and assembly machinery component) as a receptor for piecemeal degradation ...
    • Selective autophagy mediated by autophagic adapter proteins 

      Johansen, Terje; Lamark, Trond (Journal article; Tidsskriftartikkel; Peer reviewed, 2011-03-01)
      Mounting evidence suggests that autophagy is a more selective process than originally anticipated. The discovery and characterization of autophagic adapters, like p62 and NBR1, has provided mechanistic insight into this process. p62 and NBR1 are both selectively degraded by autophagy and able to act as cargo receptors for degradation of ubiquitinated subtstrates. A direct interaction between these ...