A Diversity of Selective Autophagy Receptors Determines the Specificity of the Autophagy Pathway

Kirkin, Vladimir; Rogov, Vladimir V.

doi:10.1016/j.molcel.2019.09.005

Cited by 423 publications

(401 citation statements)

References 137 publications

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“…Macroautophagy (hereafter autophagy) is a conserved intracellular degradation process that ensures cellular homeostasis by the degradation of harmful material such as damaged organelles, misfolded proteins, and bacterial pathogens. It also ensures survival of cells during starvation (Anding and Baehrecke, 2017;Gomes and Dikic, 2014;Kirkin and Rogov, 2019;Wen and Klionsky, 2016;Zaffagnini and Martens, 2016). These functions are achieved by the sequestration of the cargo material within double membrane vesicles, the autophagosomes, which form de novo around the cargo.…”

Section: Introductionmentioning

confidence: 99%

A PI3K-WIPI2 positive feedback loop allosterically activates LC3 lipidation in autophagy

Fracchiolla

Chang

Hurley

et al. 2020

Journal of Cell Biology

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Autophagy degrades cytoplasmic cargo by its delivery to lysosomes within double membrane autophagosomes. Synthesis of the phosphoinositide PI(3)P by the autophagic class III phosphatidylinositol-3 kinase complex I (PI3KC3-C1) and conjugation of ATG8/LC3 proteins to phagophore membranes by the ATG12–ATG5-ATG16L1 (E3) complex are two critical steps in autophagosome biogenesis, connected by WIPI2. Here, we present a complete reconstitution of these events. On giant unilamellar vesicles (GUVs), LC3 lipidation is strictly dependent on the recruitment of WIPI2 that in turn depends on PI(3)P. Ectopically targeting E3 to membranes in the absence of WIPI2 is insufficient to support LC3 lipidation, demonstrating that WIPI2 allosterically activates the E3 complex. PI3KC3-C1 and WIPI2 mutually promote the recruitment of each other in a positive feedback loop. When both PI 3-kinase and LC3 lipidation reactions were performed simultaneously, positive feedback between PI3KC3-C1 and WIPI2 led to rapid LC3 lipidation with kinetics similar to that seen in cellular autophagosome formation.

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Section: Introductionmentioning

confidence: 99%

A PI3K-WIPI2 positive feedback loop allosterically activates LC3 lipidation in autophagy

Fracchiolla

Chang

Hurley

et al. 2020

Journal of Cell Biology

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show abstract

“…Macroautophagy (hereafter autophagy) is a conserved intracellular degradation process that ensures cellular homeostasis by the degradation of harmful material such as damaged organelles, misfolded proteins and bacterial pathogens. It also ensures survival of cells during starvation (Anding and Baehrecke, 2017;Gomes and Dikic, 2014;Kirkin and Rogov, 2019;Wen and Klionsky, 2016;Zaffagnini and Martens, 2016). These functions are achieved by the sequestration of the cargo material within double membrane vesicles, the autophagosomes, which form de novo around the cargo.…”

Section: Introductionmentioning

confidence: 99%

A PI3K-WIPI2 positive feedback loop allosterically activates LC3 lipidation in autophagy

Fracchiolla

Chang

Hurley

et al. 2019

Preprint

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Autophagy requires the synthesis of PI(3)P and the conjugation of LC3 to the phagophore membrane. We reconstituted these two reactions and their coupling by WIPI2, and showed that positive feedback between PI3KC3-C1 and WIPI2 leads to rapid LC3 lipidation by the ATG16L1 complex. AbstractAutophagy degrades cytoplasmic cargo by its delivery to lysosomes within double membrane autophagosomes. Synthesis of the phosphoinositide PI(3)P by the autophagic PI 3-kinase complex I (PI3KC3-C1) and conjugation of ATG8/LC3 proteins to phagophore membranes by the ATG12-ATG5-ATG16L1 (E3) complex are two critical steps in autophagosome biogenesis, connected by WIPI2. Here we present a complete reconstitution of these events. On giant unilamellar vesicles (GUVs), LC3 lipidation is strictly dependent on the recruitment of WIPI2, which in turn depends on PI(3)P. Ectopically targeting E3 to membranes in the absence of WIPI2 is insufficient to support LC3 lipidation, demonstrating that WIPI2 allosterically activates the E3 complex. PI3KC3-C1 and WIPI2 mutually promote the recruitment of each other in a positive feedback loop. When both PI 3kinase and LC3 lipidation reactions were carried out simultaneously, positive feedback between PI3KC3-C1 and WIPI2 led to rapid LC3 lipidation with kinetics similar to those seen in cellular autophagosome formation. 105 132 108 125

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“…Additionally, ATG8 proteins function as hubs for selective autophagy routes, as they interact with multiple autophagy cargo receptors, mainly through an ATG8interacting motif (AIM) or a newly identified ubiquitin-interacting motif (UIM) found on the receptors [3,4,10,11]. In mammalian cells multiple cargo receptors have been identified in recent years, allowing for greater mechanistic understanding of selective autophagy processes and their impact on cellular functions and pathologies [8,[12][13][14]. However, plants lack orthologs to many of the mammalian cargo receptors, and although organelle-specific autophagy, as well as other types of selective autophagy were clearly demonstrated in plants, our mechanistic understanding of these processes and the selective cargo receptors that are required for them is still limited [3,15].…”

Section: Introductionmentioning

confidence: 99%

ATG8-interacting (ATI) 1 and 2 define a plant starvation-induced ER-phagy pathway and serve as MSBP1 (MAPR5) cargo-receptors

Michaeli

Galili

et al. 2020

Preprint

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ER-phagy, the selective autophagy of endoplasmic reticulum (ER) components, is known to operate in eukaryotes from yeast and unicellular algae to animals and plants. Thus far, only ER-stress derived ER-phagy was reported and analyzed in plants. In this study we characterize an ER-phagy pathway in Arabidopsis thaliana that is triggered by dark-induced starvation and not by ER-stress. This pathway is defined by the previously reported ATG8interacting proteins, ATI1 and ATI2 and is regulated by the TOR signaling pathway. We further identified ER-localized Membrane Steroid Binding Protein 1 (MSBP1) as an ATI1 and 2 interacting protein and an autophagy cargo, and show that ATI1 and 2 serve as its cargo receptors. Together, these findings expand our knowledge on plants responses during energy deprivation and highlight the role of this special type of ER-phagy in this process.

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A Diversity of Selective Autophagy Receptors Determines the Specificity of the Autophagy Pathway

Cited by 423 publications

References 137 publications

A PI3K-WIPI2 positive feedback loop allosterically activates LC3 lipidation in autophagy

A PI3K-WIPI2 positive feedback loop allosterically activates LC3 lipidation in autophagy

A PI3K-WIPI2 positive feedback loop allosterically activates LC3 lipidation in autophagy

ATG8-interacting (ATI) 1 and 2 define a plant starvation-induced ER-phagy pathway and serve as MSBP1 (MAPR5) cargo-receptors

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