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bioRxiv · 10.64898/2026.04.22.720228

ATG deficiency impairs stationary-phase microlipophagy through acetic acid-induced clustering of Niemann-Pick type C proteins

Tsuji, T.·Fujimoto, M.·Noda, N. N.·Fujimoto, T.
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Abstract

While the role of autophagy-related (ATG) proteins in microautophagy remains unclear, their absence in budding yeast has been reported to impair stationary-phase microlipophagy. Here, we show that this defect in ATG-deficient (atg{Delta}) cells arises not from a direct requirement of ATG proteins for the execution of microlipophagy but from accumulation of acetic acid (AA) in the medium. High concentrations of AA in the medium of atg{Delta} cells trigger the clustering of Niemann-Pick type C (NPC) proteins, causing impairment of raft-like vacuolar microdomain formation and suppression of microlipophagy. Lowering extracellular AA rapidly dissolves NPC protein clusters, restores vacuolar microdomains, and rescues microlipophagy in atg{Delta} cells. Conversely, elevating AA concentrations in the medium of wild-type cells induces NPC protein clusters and microlipophagy defects. These findings demonstrate that stationary-phase microlipophagy can proceed independently of ATG proteins and that the defect in atg{Delta} cells can be rescued by normalizing extracellular AA levels.

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Tsuji, T., Fujimoto, M., Noda, N. N., Fujimoto, T.. 2026-04-26. ATG deficiency impairs stationary-phase microlipophagy through acetic acid-induced clustering of Niemann-Pick type C proteins. https://doi.org/10.64898/2026.04.22.720228

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