bims-apauto 2023-06-04 papers

Issue of 2023–06–04
three papers selected by
Su Hyun Lee, Harvard University

Autophagy. 2023 May 27. 1-2

Bruchpiloting synaptic connections: Egfr in autophagy-mediated neuronal circuit development.

Yashveer Chohan, Emily A Eitzman, Wayne D Hawkins, Daniel J Klionsky.

Macroautophagy/autophagy is involved in many aspects of human development including the formation of neuronal circuits. A recent study from Dutta et al. found that the recruitment of Egfr (Epidermal growth factor receptor) to synapses suppresses autophagic degradation of presynaptic proteins, a requirement for proper neuronal circuit development. The findings suggest that Egfr inactivation during a distinct critical interval in late development results in increased levels of autophagy in the brain and decreased neuronal circuit development. Furthermore, the presence of brp (bruchpilot) in the synapse is critical for proper neuronal functioning over this same period. Dutta and colleagues found that increased autophagy due to Egfr inactivation results in decreased brp levels and, therefore, reduced neuronal connectivity. Through live cell imaging, it was determined that only the synaptic branches that accumulate both Egfr and brp are stabilized, allowing for the persistence of active zones, further supporting the importance of both Egfr and brp in the brain. While Dutta and colleagues collected these data based on studies conducted on Drosophila brains, the findings provide great insight as to how these different proteins may be implicated in human neurology.

Keywords: EGFR; macroautophagy; neuronal circuit development; synapse; synaptic pruning

DOI: https://doi.org/10.1080/15548627.2023.2217015

EMBO J. 2023 May 30. e112534

Selective autophagy regulates chloroplast protein import and promotes plant stress tolerance.

Chen Wan, Hui Zhang, Hongying Cheng, Robert G Sowden, Wenjuan Cai, R Paul Jarvis, Qihua Ling.

Chloroplasts are plant organelles responsible for photosynthesis and environmental sensing. Most chloroplast proteins are imported from the cytosol through the translocon at the outer envelope membrane of chloroplasts (TOC). Previous work has shown that TOC components are regulated by the ubiquitin-proteasome system (UPS) to control the chloroplast proteome, which is crucial for the organelle's function and plant development. Here, we demonstrate that the TOC apparatus is also subject to K63-linked polyubiquitination and regulation by selective autophagy, potentially promoting plant stress tolerance. We identify NBR1 as a selective autophagy adaptor targeting TOC components, and mediating their relocation into vacuoles for autophagic degradation. Such selective autophagy is shown to control TOC protein levels and chloroplast protein import and to influence photosynthetic activity as well as tolerance to UV-B irradiation and heat stress in Arabidopsis plants. These findings uncover the vital role of selective autophagy in the proteolytic regulation of specific chloroplast proteins, and how dynamic control of chloroplast protein import is critically important for plants to cope with challenging environments.

Keywords: NBR1; autophagy; chloroplast; protein import; stress response

DOI: https://doi.org/10.15252/embj.2022112534

FEBS Lett. 2023 Jun 01.

Membrane association of the ATG8 conjugation machinery emerges as a key regulatory feature for autophagosome biogenesis.

Sharon A Tooze, Wenxin Zhang, Gianmarco Lazzeri, Deepanshi Gahlot, Lipi Thukral, Roberto Covino, Taki Nishimura.

Autophagy is a highly conserved intracellular pathway which is essential for survival in all eukaryotes. In healthy cells, autophagy is used to remove damaged intracellular components, which can be as simple as unfolded proteins or as complex as whole mitochondria. Once the damaged component is captured, the autophagosome engulfs it and closes, isolating the content from the cytoplasm. The autophagosome then fuses with the late endosome and/or lysosome to deliver its content to the lysosome for degradation. Formation of the autophagosome, sequestration or capture of content, and closure all require the ATG proteins, which constitute the essential core autophagy protein machinery. This brief "nutshell" will highlight recent data revealing the importance of small membrane associated domains in the ATG proteins. In particular, recent findings from two parallel studies reveal the unexpected key role of α-helical structures in the ATG8 conjugation machinery and ATG8s. These studies illustrate how unique membrane association modules can control the formation of autophagosomes.

Keywords: ATG3; ATG8 lipidation; Amphipathic α-helix; Autophagy; MD simulation; autophagosome size; cis-membrane association; membrane expansion

DOI: https://doi.org/10.1002/1873-3468.14676