The Role of ATG9 Vesicles in Autophagosome Biogenesis

Holzer, Elisabeth; Martens, Sascha; Tulli, Susanna

doi:10.1016/j.jmb.2024.168489

Cited by 15 publications

(1 citation statement)

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“…The biogenesis of autophagosomes is mediated by a set of conserved factors referred to as the autophagy machinery ( Chang et al, 2021 ; Mizushima et al, 2011 ; Nishimura and Tooze, 2020 ; Xie and Klionsky, 2007 ). Over the past years, a consensus model for how this machinery acts to mediate the formation and expansion of phagophores has emerged ( Holzer et al, 2024 ). According to this model, phagophore formation is initiated in proximity to the endoplasmic reticulum (ER) by membrane precursors containing the lipid scramblase Atg9 ( Axe et al, 2008 ; Bieber et al, 2022 ; Gómez-Sánchez et al, 2018 ; Graef et al, 2013 ; Hayashi-Nishino et al, 2009 ; Suzuki et al, 2013 ; Yamamoto et al, 2012 ; Ylä-Anttila et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

Faa1 membrane binding drives positive feedback in autophagosome biogenesis via fatty acid activation

Baumann,

Achleitner,

Tulli

et al. 2024

Journal of Cell Biology

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Autophagy serves as a stress response pathway by mediating the degradation of cellular material within lysosomes. In autophagy, this material is encapsulated in double-membrane vesicles termed autophagosomes, which form from precursors referred to as phagophores. Phagophores grow by lipid influx from the endoplasmic reticulum into Atg9-positive compartments and local lipid synthesis provides lipids for their expansion. How phagophore nucleation and expansion are coordinated with lipid synthesis is unclear. Here, we show that Faa1, an enzyme activating fatty acids, is recruited to Atg9 vesicles by directly binding to negatively charged membranes with a preference for phosphoinositides such as PI3P and PI4P. We define the membrane-binding surface of Faa1 and show that its direct interaction with the membrane is required for its recruitment to phagophores. Furthermore, the physiological localization of Faa1 is key for its efficient catalysis and promotes phagophore expansion. Our results suggest a positive feedback loop coupling phagophore nucleation and expansion to lipid synthesis.

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Section: Introductionmentioning

confidence: 99%

Faa1 membrane binding drives positive feedback in autophagosome biogenesis via fatty acid activation

Baumann,

Achleitner,

Tulli

et al. 2024

Journal of Cell Biology

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Neues zur Struktur und Funktion von ATG9-Vesikeln in Synapsen

Binotti,

Sambandan,

Jahn

2024

Biospektrum

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Neurons communicate via release of neurotransmitters at synapses, which requires hundreds of different proteins. Here, autophagy plays a key role in protein maintenance and degradation, with vesicles containing the protein ATG9 being crucial for the formation of autophagosomes. We found that these vesicles, while resembling synaptic vesicles in size and density, represent a separate and heterogeneous vesicle population in the synapse. They serve as a platform for the recruitment and assembly of various effector proteins required for interaction with different intracellular organelles.

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