Alf Håkon Lystad

• 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 (2019). NIPSNAP1 and NIPSNAP2 act as “eat-me signal” for mitophagy. Developmental Cell.  ISSN 1534-5807.  49(4), s 509- 525.e12 . doi: 10.1016/j.devcel.2019.03.013 Full text in Research Archive.
• Herhaus, Lina; Bhaskara, Ramachandra M; Lystad, Alf Håkon; Gestal-Mato, Uxia; Covarrubias-Pinto, Adriana; Bonn, Florian; Simonsen, Anne; Hummer, Gerhard & Dikic, Ivan (2019). TBK1-mediated phosphorylation of LC3C and GABARAP-L2 controls autophagosome shedding by ATG4 protease. EMBO Reports.  ISSN 1469-221X. . doi: 10.15252/embr.201948317
• Herzog, Laura K; Kevei, Eva; Marchante, Ricardo; Botther, Claudia; Bindesbøll, Christian; Lystad, Alf Håkon; Pfeiffer, Annika; Gierisch, Maria; Salomons, Florian; Simonsen, Anne; Hoppe, Thorsten & Dantuma, Nico P (2019). The Machado-Joseph disease deubiquitylase ataxin-3 interacts with LC3C/GABARAP and promotes autophagy.. Aging Cell.  ISSN 1474-9718. . doi: 10.1111/acel.13051 Show summary

  The pathology of spinocerebellar ataxia type 3, also known as Machado‐Joseph disease, is triggered by aggregation of toxic ataxin‐3 (ATXN3) variants containing expanded polyglutamine repeats. The physiological role of this deubiquitylase, however, remains largely unclear. Our recent work showed that ATX‐3, the nematode orthologue of ATXN3, together with the ubiquitin‐directed segregase CDC‐48, regulates longevity in Caenorhabditis elegans. Here, we demonstrate that the long‐lived cdc‐48.1; atx‐3 double mutant displays reduced viability under prolonged starvation conditions that can be attributed to the loss of catalytically active ATX‐3. Reducing the levels of the autophagy protein BEC‐1 sensitized worms to the effect of ATX‐3 deficiency, suggesting a role of ATX‐3 in autophagy. In support of this conclusion, the depletion of ATXN3 in human cells caused a reduction in autophagosomal degradation of proteins. Surprisingly, reduced degradation in ATXN3‐depleted cells coincided with an increase in the number of autophagosomes while levels of lipidated LC3 remained unaffected. We identified two conserved LIR domains in the catalytic Josephin domain of ATXN3 that directly interacted with the autophagy adaptors LC3C and GABARAP in vitro. While ATXN3 localized to early autophagosomes, it was not subject to lysosomal degradation, suggesting a transient regulatory interaction early in the autophagic pathway. We propose that the deubiquitylase ATX‐3/ATXN3 stimulates autophagic degradation by preventing superfluous initiation of autophagosomes, thereby promoting an efficient autophagic flux important to survive starvation.

• Lystad, Alf Håkon; Carlsson, Sven R; Rodriguez de la Ballina, Laura; Kauffman, Karlina J; Nag, Shanta; Yoshimori, Tamotsu; Melia, Thomas J & Simonsen, Anne (2019). Distinct functions of ATG16L1 isoforms in membrane binding and LC3B lipidation in autophagy-related processes. Nature Cell Biology.  ISSN 1465-7392.  21(3), s 372- 383 . doi: 10.1038/s41556-019-0274-9
• Lystad, Alf Håkon & Simonsen, Anne (2019). Mechanisms and Pathophysiological Roles of the ATG8 Conjugation Machinery. Cells.  ISSN 2073-4409.  8(9), s 973 . doi: 10.3390/cells8090973 Show summary

  Since their initial discovery around two decades ago, the yeast autophagy-related (Atg)8 protein and its mammalian homologues of the light chain 3 (LC3) and γ-aminobutyric acid receptor associated proteins (GABARAP) families have been key for the tremendous expansion of our knowledge about autophagy, a process in which cytoplasmic material become targeted for lysosomal degradation. These proteins are ubiquitin-like proteins that become directly conjugated to a lipid in the autophagy membrane upon induction of autophagy, thus providing a marker of the pathway, allowing studies of autophagosome biogenesis and maturation. Moreover, the ATG8 proteins function to recruit components of the core autophagy machinery as well as cargo for selective degradation. Importantly, comprehensive structural and biochemical in vitro studies of the machinery required for ATG8 protein lipidation, as well as their genetic manipulation in various model organisms, have provided novel insight into the molecular mechanisms and pathophysiological roles of the mATG8 proteins. Recently, it has become evident that the ATG8 proteins and their conjugation machinery are also involved in intracellular pathways and processes not related to autophagy. This review focuses on the molecular functions of ATG8 proteins and their conjugation machinery in autophagy and other pathways, as well as their links to disease.

• Kauffman, Karlina J; Yu, Shenliang; Jin, Jiaxin; Mugo, Brian; Nguyen, Nathan; O'Brien, Aidan; Nag, Shanta; Lystad, Alf Håkon & Melia, Thomas J (2018). Delipidation of mammalian Atg8-family proteins by each of the four ATG4 proteases. Autophagy.  ISSN 1554-8627.  14(6), s 992- 1010 . doi: 10.1080/15548627.2018.1437341
• Dragich, Joanna M; Kuwajima, Takaaki; Hirose-Ikeda, Megumi; Yoon, Michael S; Eenjes, Evelien; Bosco, Joan R; Fox, Leora M; Lystad, Alf Håkon; Oo, Tinmarla F; Yarygina, Olga; Mita, Tomohiro; Waguri, Satoshi; Ichimura, Yoshinobu; Komatsu, Masaaki; Simonsen, Anne; Burke, Robert E; Mason, Carol A & Yamamoto, Ai (2016). Autophagy linked FYVE (Alfy/WDFY3) is required for establishing neuronal connectivity in the mammalian brain. eLIFE.  ISSN 2050-084X.  5(September) . doi: 10.7554/eLife.14810
• Holland, Petter; Knævelsrud, Helene; Søreng, Kristiane; Mathai, Benan John; Lystad, Alf Håkon; Pankiv, Serhiy; Bjørndal, Gunnveig Toft; Schultz, Sebastian; Lobert, Viola; Chan, Robin B; Zhou, Bowen; Liestøl, Knut; Carlsson, Sven R; Melia, Thomas J; Di Paolo, Gilbert & Simonsen, Anne (2016). HS1BP3 negatively regulates autophagy by modulation of phosphatidic acid levels. Nature Communications.  ISSN 2041-1723.  7 . doi: 10.1038/ncomms13889 Full text in Research Archive.
• Lystad, Alf Håkon & Simonsen, Anne (2016). Phosphoinositide-binding proteins in autophagy. FEBS Letters.  ISSN 0014-5793.  s 2454- 2468 . doi: 10.1002/1873-3468.12286
• Lystad, Alf Håkon & Simonsen, Anne (2015). Assays to monitor aggrephagy. Methods.  ISSN 1046-2023.  75, s 112- 119 . doi: 10.1016/j.ymeth.2014.12.019
• Lystad, Alf Håkon; Ichimura, Yoshinobu; Takagi, K; Yang, Yinjie; Pankiv, Serhiy; Kanegae, Yumi; Kageyama, Shun; Suzuki, Mariko; Saito, Izumu; Mizushima, Tsunehiro; Komatsu, Masaaki & Simonsen, Anne (2014). Structural determinants in GABARAP required for the selective binding and recruitment of ALFY to LC3B-positive structures. EMBO Reports.  ISSN 1469-221X.  15(5), s 557- 565 . doi: 10.1002/embr.201338003
• Isakson, Pauline; Lystad, Alf Håkon; Breen, Kamilla; Koster, Gerbrand; Stenmark, Harald Alfred & Simonsen, Anne (2013). TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody ring degradation by selective autophagy. Autophagy.  ISSN 1554-8627.  9(12), s 1955- 1964 . doi: 10.4161/auto.26085

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• Lystad, Alf Håkon; Carlsson, Sven R. & Simonsen, Anne (2019). Toward the function of mammalian ATG12-ATG5-ATG16L1 complex in autophagy and related processes. Autophagy.  ISSN 1554-8627.  15(8), s 1485- 1486 . doi: 10.1080/15548627.2019.1618100 Show summary

  The machinery that decorates autophagic membranes with lipid-conjugated LC3/GABARAP is not yet fully understood. We recently reported the purification of the full-length ATG12–ATG5-ATG16L1 complex, and in reconstitution experiments with purified ATG7, ATG3, and LC3/GABARAP in vitro, together with rescue experiments in knockout cells, important aspects of the complete lipidation reaction were revealed. Hitherto unobserved membrane-binding regions in ATG16L1 were found, contributing to properties that explain the crucial role of this protein in membrane targeting and LC3/GABARAP lipidation in macroautophagy/autophagy and other related processes.

• Lystad, Alf Håkon; Sporstol, Marita; Foroughi, Masoud; Roos, Norbert; Berg, Trond & Eskild, Winnie (2009). Regulation of VEGF expression by vitamin D i hepatic stellate cells - possible attenuation by the nuclear receptor coregulator NCY-G1.
• Lystad, Alf Håkon; Sporstol, Marita; Foroughi, Masoud; Roos, Norbert; Berg, Trond & Eskild, Winnie (2009). Regulation of VEGF expression by vitamin D in hepatic stellate cells - possible attenuation by the nuclear receptor coregulator NCU-G1.

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