Parallel phospholipid transfer by Vps13 and Atg2 determines autophagosome biogenesis dynamics

Area of Science:

• Cell biology
• Molecular and cell biology
• Biochemistry

Background:

• Autophagy is a fundamental cellular process involving the formation of double-membrane autophagosomes.
• Phospholipid transfer (PLT) across endoplasmic reticulum (ER)-phagophore contact sites (PERCS) is crucial for autophagosome biogenesis.
• Atg2 was the only known PLT protein driving phagophore expansion in vivo.

Purpose of the Study:

• To investigate the role of Atg2 and other proteins in phospholipid transfer during autophagosome biogenesis.
• To determine the rate-limiting steps and molecular mechanisms of phagophore expansion.
• To explore the cooperative function of PLT proteins in membrane assembly.

Main Methods:

• Quantitative live-cell imaging in yeast.
• Analysis of Atg2 and Vps13 localization and function at PERCS.
• Measurement of autophagosome size and duration during starvation.

Main Results:

• A poor correlation was observed between Atg2 levels at PERCS and autophagosome size/duration.
• Vps13, a PLT protein, localizes to the phagophore rim and promotes expansion in parallel with Atg2.
• Atg2-mediated PLT is non-rate-limiting when Vps13 is present; Vps13 absence makes Atg2 rate-limiting.

Conclusions:

• Conserved PLT proteins, like Atg2 and Vps13, cooperate to channel phospholipids for autophagosome biogenesis.
• Membrane assembly during autophagosome formation is non-rate-limiting due to the coordinated action of PLT proteins.
• This cooperative mechanism ensures efficient membrane expansion for autophagosome biogenesis.