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Two Distinct Pathways for Targeting Proteins from the Cytoplasm to the Vacuole/Lysosome

Baba, Misuzu, Osumi, Masako, Scott, Sidney V., Klionsky, Daniel J., Ohsumi, Yoshinori·1997·The Journal of Cell Biology
DOI 10.1083/jcb.139.7.1687PMC PMC2132654
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Abstract

Stress conditions lead to a variety of physiological responses at the cellular level. Autophagy is an essential process used by animal, plant, and fungal cells that allows for both recycling of macromolecular constituents under conditions of nutrient limitation and remodeling the intracellular structure for cell differentiation. To elucidate the molecular basis of autophagic protein transport to the vacuole/lysosome, we have undertaken a morphological and biochemical analysis of this pathway in yeast. Using the vacuolar hydrolase aminopeptidase I (API) as a marker, we provide evidence that the autophagic pathway overlaps with the biosynthetic pathway, cytoplasm to vacuole targeting (Cvt), used for API import. Before targeting, the precursor form of API is localized mostly in restricted regions of the cytosol as a complex with spherical particles (termed Cvt complex). During vegetative growth, the Cvt complex is selectively wrapped by a membrane sac forming a double membrane-bound structure of ∼150 nm diam, which then fuses with the vacuolar membrane. This process is topologically the same as macroautophagy induced under starvation conditions in yeast (Baba, M., K. Takeshige, N. Baba, and Y. Ohsumi. 1994. J. Cell Biol. 124:903–913). However, in contrast with autophagy, API import proceeds constitutively in growing conditions. This is the first demonstration of the use of an autophagy-like mechanism for biosynthetic delivery of a vacuolar hydrolase. Another important finding is that when cells are subjected to starvation conditions, the Cvt complex is now taken up by an autophagosome that is much larger and contains other cytosolic components; depending on environmental conditions, the cell uses an alternate pathway to sequester the Cvt complex and selectively deliver API to the vacuole. Together these results indicate that two related but distinct autophagy-like processes are involved in both biogenesis of vacuolar resident proteins and sequestration of substrates to be degraded.

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Research works printed but not linked: 31

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Metadata

Authors
Baba, M., Osumi, M., Scott, S. V., Klionsky, D. J., & Ohsumi, Y.
Affiliations
*Department of Cell Biology, National Institute for Basic Biology, Okazaki 444, Japan; ‡Department of Chemical and Biological Sciences, Faculty of Science, Japan Women's University, Mejirodai, Tokyo 112, Japan; and §Section of Microbiology, University of California, Davis, California 95616
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
1997-12-29
Volume
139
Issue
7
Pages
1687-1695
ISSN
  • 0021-9525
  • 1540-8140
DOI
10.1083/jcb.139.7.1687
PMC
PMC2132654
Cited by
292
References
0
Language
en

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