Small Trafficking Inhibitor Retro-2 Disrupts the Microtubule-Dependent Trafficking of Autophagic Vacuoles

Abstract

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Autophagy is a catabolic recycling process by which a cell degrades its own constituents to contribute to cell homeostasis or survival. We report that the small trafficking inhibitor Retro-2 impairs microtubule-dependent vacuolar trafficking in autophagy. Retro-2 induced autophagy and promoted the dramatic cytoplasmic accumulation of large autophagosomes. Moreover, Retro-2 decreased the spreading of autophagosomes within the cytoplasm of nutrient-starved cells. In addition, Retro-2 abolished autolysosomes formation. We show that these effects arise from hitherto unsuspected disassembly activity of the small molecule on the cellular microtubule network, which is known to act as a key regulator of vacuolar trafficking of the autophagy pathway.

Keywords

• autophagy
• nutrient starvation
• microtubules
• vacuolar trafficking
• autophagosome
• autolysosome