Rim aperture of yeast autophagic membranes balances cargo inclusion with vesicle maturation

Oren Shatz; Milana Fraiberg; Damilola Isola; Shubhankar Das; Olee Gogoi; Alexandra Polyansky; Eyal Shimoni; Tali Dadosh; Nili Dezorella; Sharon G. Wolf; Zvulun Elazar

doi:10.1016/j.devcel.2024.02.002

Rim aperture of yeast autophagic membranes balances cargo inclusion with vesicle maturation

Oren Shatz, Milana Fraiberg, Damilola Isola, Shubhankar Das, Olee Gogoi, Alexandra Polyansky, Eyal Shimoni, Tali Dadosh, Nili Dezorella, Sharon G. Wolf, Zvulun Elazar^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

Autophagy eliminates cytoplasmic material by engulfment in membranous vesicles targeted for lysosome degradation. Nonselective autophagy coordinates sequestration of bulk cargo with the growth of the isolation membrane (IM) in a yet-unknown manner. Here, we show that in the budding yeast Saccharomyces cerevisiae, IMs expand while maintaining a rim sufficiently wide for sequestration of large cargo but tight enough to mature in due time. An obligate complex of Atg24/Snx4 with Atg20 or Snx41 assembles locally at the rim in a spatially extended manner that specifically depends on autophagic PI(3)P. This assembly stabilizes the open rim to promote autophagic sequestration of large cargo in correlation with vesicle expansion. Moreover, constriction of the rim by the PI(3)P-dependent Atg2-Atg18 complex and clearance of PI(3)P by Ymr1 antagonize rim opening to promote autophagic maturation and consumption of small cargo. Tight regulation of membrane rim aperture by PI(3)P thus couples the mechanism and physiology of nonselective autophagy.

Original language	English
Pages (from-to)	911-923.e4
Journal	Developmental Cell
Volume	59
Issue number	7
DOIs	https://doi.org/10.1016/j.devcel.2024.02.002
Publication status	Published Online - 5 Mar 2024

Bibliographical note

Z.E. is the incumbent of the Harold Korda Chair of Biology. We are grateful for funding from the Israel Science Foundation (grant #215/19), Joint NRF - ISF Research Fund (grant #3221/19), Joint NSFC-ISF Research Fund (grant # 3345/20), and the Yeda-Sela Center for Basic Research. We thank Olena Trofimyuk and other members of the Elazar group for their experimental support. Leica HyVolution confocal and STED images were acquired at the Advanced Optical Imaging Unit, de Picciotto-Lesser Cell Observatory unit at the Moross Integrated Cancer Center Life Science Core Facilities, The Weizmann Institute of Science. HPF-FS CLEM microscopy was performed at the Irving and Cherna Moskowitz Center for Nano and Bio-Nano Imaging, The Weizmann Institute of Science. We thank Yoseph Addadi for HyVolution imaging and Katya Rechav for FIB-SEM imaging. We thank Claudine Kraft, Bernd Bukau, Maya Schuldiner, Hitoshi Nakatogawa, Michael Thumm, and Fulvio Reggiori for kind gifts of plasmids (as indicated in Table S1, “plasmids”) and Luke Lavis for the kind gift of Halo-JF635. Co-author Dr. Eyal Shimoni has been deeply committed and contributed greatly to the course of this study and has passed away in its final stages. We publish this manuscript in his loving memory. May he rest in peace.

Publisher Copyright:
© 2024 Elsevier Inc.

All Science Journal Classification (ASJC) codes

Molecular Biology
General Biochemistry,Genetics and Molecular Biology
Developmental Biology
Cell Biology

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10.1016/j.devcel.2024.02.002

Cite this

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title = "Rim aperture of yeast autophagic membranes balances cargo inclusion with vesicle maturation",

abstract = "Autophagy eliminates cytoplasmic material by engulfment in membranous vesicles targeted for lysosome degradation. Nonselective autophagy coordinates sequestration of bulk cargo with the growth of the isolation membrane (IM) in a yet-unknown manner. Here, we show that in the budding yeast Saccharomyces cerevisiae, IMs expand while maintaining a rim sufficiently wide for sequestration of large cargo but tight enough to mature in due time. An obligate complex of Atg24/Snx4 with Atg20 or Snx41 assembles locally at the rim in a spatially extended manner that specifically depends on autophagic PI(3)P. This assembly stabilizes the open rim to promote autophagic sequestration of large cargo in correlation with vesicle expansion. Moreover, constriction of the rim by the PI(3)P-dependent Atg2-Atg18 complex and clearance of PI(3)P by Ymr1 antagonize rim opening to promote autophagic maturation and consumption of small cargo. Tight regulation of membrane rim aperture by PI(3)P thus couples the mechanism and physiology of nonselective autophagy.",

author = "Oren Shatz and Milana Fraiberg and Damilola Isola and Shubhankar Das and Olee Gogoi and Alexandra Polyansky and Eyal Shimoni and Tali Dadosh and Nili Dezorella and Wolf, {Sharon G.} and Zvulun Elazar",

note = "Z.E. is the incumbent of the Harold Korda Chair of Biology. We are grateful for funding from the Israel Science Foundation (grant #215/19), Joint NRF - ISF Research Fund (grant #3221/19), Joint NSFC-ISF Research Fund (grant # 3345/20), and the Yeda-Sela Center for Basic Research. We thank Olena Trofimyuk and other members of the Elazar group for their experimental support. Leica HyVolution confocal and STED images were acquired at the Advanced Optical Imaging Unit, de Picciotto-Lesser Cell Observatory unit at the Moross Integrated Cancer Center Life Science Core Facilities, The Weizmann Institute of Science. HPF-FS CLEM microscopy was performed at the Irving and Cherna Moskowitz Center for Nano and Bio-Nano Imaging, The Weizmann Institute of Science. We thank Yoseph Addadi for HyVolution imaging and Katya Rechav for FIB-SEM imaging. We thank Claudine Kraft, Bernd Bukau, Maya Schuldiner, Hitoshi Nakatogawa, Michael Thumm, and Fulvio Reggiori for kind gifts of plasmids (as indicated in Table S1, “plasmids”) and Luke Lavis for the kind gift of Halo-JF635. Co-author Dr. Eyal Shimoni has been deeply committed and contributed greatly to the course of this study and has passed away in its final stages. We publish this manuscript in his loving memory. May he rest in peace. Publisher Copyright: {\textcopyright} 2024 Elsevier Inc.",

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T1 - Rim aperture of yeast autophagic membranes balances cargo inclusion with vesicle maturation

AU - Shatz, Oren

AU - Fraiberg, Milana

AU - Isola, Damilola

AU - Das, Shubhankar

AU - Gogoi, Olee

AU - Polyansky, Alexandra

AU - Shimoni, Eyal

AU - Dadosh, Tali

AU - Dezorella, Nili

AU - Wolf, Sharon G.

AU - Elazar, Zvulun

N1 - Z.E. is the incumbent of the Harold Korda Chair of Biology. We are grateful for funding from the Israel Science Foundation (grant #215/19), Joint NRF - ISF Research Fund (grant #3221/19), Joint NSFC-ISF Research Fund (grant # 3345/20), and the Yeda-Sela Center for Basic Research. We thank Olena Trofimyuk and other members of the Elazar group for their experimental support. Leica HyVolution confocal and STED images were acquired at the Advanced Optical Imaging Unit, de Picciotto-Lesser Cell Observatory unit at the Moross Integrated Cancer Center Life Science Core Facilities, The Weizmann Institute of Science. HPF-FS CLEM microscopy was performed at the Irving and Cherna Moskowitz Center for Nano and Bio-Nano Imaging, The Weizmann Institute of Science. We thank Yoseph Addadi for HyVolution imaging and Katya Rechav for FIB-SEM imaging. We thank Claudine Kraft, Bernd Bukau, Maya Schuldiner, Hitoshi Nakatogawa, Michael Thumm, and Fulvio Reggiori for kind gifts of plasmids (as indicated in Table S1, “plasmids”) and Luke Lavis for the kind gift of Halo-JF635. Co-author Dr. Eyal Shimoni has been deeply committed and contributed greatly to the course of this study and has passed away in its final stages. We publish this manuscript in his loving memory. May he rest in peace. Publisher Copyright: © 2024 Elsevier Inc.

PY - 2024/3/5

Y1 - 2024/3/5

N2 - Autophagy eliminates cytoplasmic material by engulfment in membranous vesicles targeted for lysosome degradation. Nonselective autophagy coordinates sequestration of bulk cargo with the growth of the isolation membrane (IM) in a yet-unknown manner. Here, we show that in the budding yeast Saccharomyces cerevisiae, IMs expand while maintaining a rim sufficiently wide for sequestration of large cargo but tight enough to mature in due time. An obligate complex of Atg24/Snx4 with Atg20 or Snx41 assembles locally at the rim in a spatially extended manner that specifically depends on autophagic PI(3)P. This assembly stabilizes the open rim to promote autophagic sequestration of large cargo in correlation with vesicle expansion. Moreover, constriction of the rim by the PI(3)P-dependent Atg2-Atg18 complex and clearance of PI(3)P by Ymr1 antagonize rim opening to promote autophagic maturation and consumption of small cargo. Tight regulation of membrane rim aperture by PI(3)P thus couples the mechanism and physiology of nonselective autophagy.

AB - Autophagy eliminates cytoplasmic material by engulfment in membranous vesicles targeted for lysosome degradation. Nonselective autophagy coordinates sequestration of bulk cargo with the growth of the isolation membrane (IM) in a yet-unknown manner. Here, we show that in the budding yeast Saccharomyces cerevisiae, IMs expand while maintaining a rim sufficiently wide for sequestration of large cargo but tight enough to mature in due time. An obligate complex of Atg24/Snx4 with Atg20 or Snx41 assembles locally at the rim in a spatially extended manner that specifically depends on autophagic PI(3)P. This assembly stabilizes the open rim to promote autophagic sequestration of large cargo in correlation with vesicle expansion. Moreover, constriction of the rim by the PI(3)P-dependent Atg2-Atg18 complex and clearance of PI(3)P by Ymr1 antagonize rim opening to promote autophagic maturation and consumption of small cargo. Tight regulation of membrane rim aperture by PI(3)P thus couples the mechanism and physiology of nonselective autophagy.

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U2 - 10.1016/j.devcel.2024.02.002

DO - 10.1016/j.devcel.2024.02.002

M3 - Article

C2 - 38447569

AN - SCOPUS:85188439764

SN - 1534-5807

VL - 59

SP - 911-923.e4

JO - Developmental Cell

JF - Developmental Cell

IS - 7

ER -

Rim aperture of yeast autophagic membranes balances cargo inclusion with vesicle maturation

Abstract

Bibliographical note

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