1. Cell Biology

Atg1 kinase in fission yeast is activated by Atg11-mediated dimerization and cis-autophosphorylation

  1. Zhao-Qian Pan
  2. Guang-Can Shao
  3. Xiao-Man Liu
  4. Quan Chen
  5. Meng-Qiu Dong
  6. Li-Lin Du  Is a corresponding author
  1. National Institute of Biological Sciences, China
https://doi.org/10.7554/eLife.58073
Share this article
Cite this article
  1. Zhao-Qian Pan
  2. Guang-Can Shao
  3. Xiao-Man Liu
  4. Quan Chen
  5. Meng-Qiu Dong
  6. Li-Lin Du
(2020)
Atg1 kinase in fission yeast is activated by Atg11-mediated dimerization and cis-autophosphorylation
eLife 9:e58073.
https://doi.org/10.7554/eLife.58073
  2. Download BibTeX
  3. Download .RIS

Abstract

Autophagy is a proteolytic pathway conserved from yeasts to mammals. Atg1 kinase is essential for autophagy but how its activity is controlled remains insufficiently understood. Here, we show that, in the fission yeast Schizosaccharomyces pombe, Atg1 kinase activity requires Atg11, the ortholog of mammalian FIP200/RB1CC1, but does not require Atg13, Atg17, or Atg101. Remarkably, a 62-amino-acid region of Atg11 is sufficient for the autophagy function of Atg11 and for supporting the Atg1 kinase activity. This region harbors an Atg1-binding domain and a homodimerization domain. Dimerizing Atg1 is the main role of Atg11, as it can be bypassed by artificially dimerizing Atg1. In an Atg1 dimer, only one Atg1 molecule needs to be catalytically active, suggesting that Atg1 activation can be achieved through cis-autophosphorylation. We propose that mediating Atg1 oligomerization and activation may be a conserved function of Atg11/FIP200 family proteins and cis-autophosphorylation may be a general mechanism of Atg1 activation.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Zhao-Qian Pan

    National Institute of Biological Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0346-0259

  2. Guang-Can Shao

    National Institute of Biological Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  3. Xiao-Man Liu

    National Institute of Biological Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9968-3988

  4. Quan Chen

    National Institute of Biological Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  5. Meng-Qiu Dong

    National Institute of Biological Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6094-1182

  6. Li-Lin Du

    National Institute of Biological Sciences, Beijing, China
    For correspondence
    dulilin@nibs.ac.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1028-7397

Funding

National Basic Research Program of China (2014CB849901)

  • Li-Lin Du

National Basic Research Program of China (2014CB849801)

  • Meng-Qiu Dong

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Claudine Kraft, University of Freiburg, Germany

Version history

  1. Received: April 20, 2020
  2. Accepted: September 10, 2020
  3. Accepted Manuscript published: September 10, 2020 (version 1)
  4. Version of Record published: September 23, 2020 (version 2)

Copyright

© 2020, Pan et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,654
    Page views
  • 325
    Downloads
  • 19
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Zhao-Qian Pan
  2. Guang-Can Shao
  3. Xiao-Man Liu
  4. Quan Chen
  5. Meng-Qiu Dong
  6. Li-Lin Du
(2020)
Atg1 kinase in fission yeast is activated by Atg11-mediated dimerization and cis-autophosphorylation
eLife 9:e58073.
https://doi.org/10.7554/eLife.58073

Share this article

https://doi.org/10.7554/eLife.58073

Categories and tags

Research organism

Further reading

    1. Cell Biology
    2. Chromosomes and Gene Expression

    Heat stress impairs centromere structure and segregation of meiotic chromosomes in Arabidopsis

    Lucie Crhak Khaitova, Pavlina Mikulkova ... Karel Riha
    Research Article

    Heat stress is a major threat to global crop production, and understanding its impact on plant fertility is crucial for developing climate-resilient crops. Despite the known negative effects of heat stress on plant reproduction, the underlying molecular mechanisms remain poorly understood. Here, we investigated the impact of elevated temperature on centromere structure and chromosome segregation during meiosis in Arabidopsis thaliana. Consistent with previous studies, heat stress leads to a decline in fertility and micronuclei formation in pollen mother cells. Our results reveal that elevated temperature causes a decrease in the amount of centromeric histone and the kinetochore protein BMF1 at meiotic centromeres with increasing temperature. Furthermore, we show that heat stress increases the duration of meiotic divisions and prolongs the activity of the spindle assembly checkpoint during meiosis I, indicating an impaired efficiency of the kinetochore attachments to spindle microtubules. Our analysis of mutants with reduced levels of centromeric histone suggests that weakened centromeres sensitize plants to elevated temperature, resulting in meiotic defects and reduced fertility even at moderate temperatures. These results indicate that the structure and functionality of meiotic centromeres in Arabidopsis are highly sensitive to heat stress, and suggest that centromeres and kinetochores may represent a critical bottleneck in plant adaptation to increasing temperatures.

    1. Cell Biology

    High-altitude hypoxia exposure inhibits erythrophagocytosis by inducing macrophage ferroptosis in the spleen

    Wan-ping Yang, Mei-qi Li ... Qian-qian Luo
    Research Article

    High-altitude polycythemia (HAPC) affects individuals living at high altitudes, characterized by increased red blood cells (RBCs) production in response to hypoxic conditions. The exact mechanisms behind HAPC are not fully understood. We utilized a mouse model exposed to hypobaric hypoxia (HH), replicating the environmental conditions experienced at 6000 m above sea level, coupled with in vitro analysis of primary splenic macrophages under 1% O2 to investigate these mechanisms. Our findings indicate that HH significantly boosts erythropoiesis, leading to erythrocytosis and splenic changes, including initial contraction to splenomegaly over 14 days. A notable decrease in red pulp macrophages (RPMs) in the spleen, essential for RBCs processing, was observed, correlating with increased iron release and signs of ferroptosis. Prolonged exposure to hypoxia further exacerbated these effects, mirrored in human peripheral blood mononuclear cells. Single-cell sequencing showed a marked reduction in macrophage populations, affecting the spleen’s ability to clear RBCs and contributing to splenomegaly. Our findings suggest splenic ferroptosis contributes to decreased RPMs, affecting erythrophagocytosis and potentially fostering continuous RBCs production in HAPC. These insights could guide the development of targeted therapies for HAPC, emphasizing the importance of splenic macrophages in disease pathology.

    1. Cell Biology

    Golgi Apparatus: Making progress

    Jurgen Denecke
    Insight

    Mapping proteins in and associated with the Golgi apparatus reveals how this cellular compartment emerges in budding yeast and progresses over time.