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Cited by 338

The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.

ESCRTs and Fab1 Regulate Distinct Steps of Autophagy

Open access
Rusten, Tor Erik, Vaccari, Thomas, Lindmo, Karine, Rodahl, Lina M.W., Nezis, Ioannis P., Sem-Jacobsen, Catherine, Wendler, Franz, Vincent, Jean-Paul, Brech, Andreas, Bilder, David, Stenmark, Harald·2007·Current Biology

Abstract

Eukaryotes use autophagy to turn over organelles, protein aggregates, and cytoplasmic constituents. The impairment of autophagy causes developmental defects, starvation sensitivity, the accumulation of protein aggregates, neuronal degradation, and cell death [1, 2]. Double-membraned autophagosomes sequester cytoplasm and fuse with endosomes or lysosomes in higher eukaryotes [3], but the importance of the endocytic pathway for autophagy and associated disease is not known. Here, we show that regulators of endosomal biogenesis and functions play a critical role in autophagy in Drosophila melanogaster. Genetic and ultrastructural analysis showed that subunits of endosomal sorting complex required for transport (ESCRT)-I, -II and -III, as well as their regulatory ATPase Vps4 and the endosomal PtdIns(3)P 5-kinase Fab1, all are required for autophagy. Although the loss of ESCRT or Vps4 function caused the accumulation of autophagosomes, probably because of inhibited fusion with the endolysosomal system, Fab1 activity was necessary for the maturation of autolysosomes. Importantly, reduced ESCRT functions aggravated polyglutamine-induced neurotoxicity in a model for Huntington's disease. Thus, this study links ESCRT function with autophagy and aggregate-induced neurodegeneration, thereby providing a plausible explanation for the fact that ESCRT mutations are involved in inherited neurodegenerative disease in humans [4].

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Metadata

Authors
Rusten, T. E., Vaccari, T., Lindmo, K., Rodahl, L. M. W., Nezis, I. P., Sem-Jacobsen, C., Wendler, F., Vincent, J.-P., Brech, A., Bilder, D., & Stenmark, H.
Venue
Current Biology
Publisher
Elsevier BV
Published
2007-10
Volume
17
Issue
20
Pages
1817-1825
ISSN
0960-9822 (ISSN-L)
OpenAlex
W2060579362
Cited by
338
References
46
FWCI
12.98
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: ESCRTs and Fab1 Regulate Distinct Steps of Autophagy. https://app.cochat.ai/papers/10.1016/j.cub.2007.09.032
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Rusten, T. E., Vaccari, T., Lindmo, K., Rodahl, L. M. W., Nezis, I. P., Sem-Jacobsen, C., Wendler, F., Vincent, J.-P., Brech, A., Bilder, D., & Stenmark, H. (2007). ESCRTs and Fab1 Regulate Distinct Steps of Autophagy. Current Biology. https://doi.org/10.1016/j.cub.2007.09.032

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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