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Altered lipid content inhibits autophagic vesicular fusion

Koga, Hiroshi, Kaushik, Susmita, Cuervo, Ana Maria·2010·The FASEB Journal
DOI 10.1096/fj.09-144519
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Abstract

The autophagic/lysosomal system includes a variety of vesicular compartments that undergo dynamic fusion events. However, the characteristics and factors modulating these interactions remain, for the most part, unknown. To gain insights on the properties that govern lysosomal fusion events, we have established an in vitro fusion assay using different lysosomal/autophagic compartments isolated from mouse liver. We have found that autophagosome/lysosome fusion is a temperature‐dependent process (fusion increment of 0.2±0.01%/°C), which requires ATP (1–3 mM), GTP (1–2 mM), Ca 2+ (0.2–2 mM), and an acidic lysosomal pH (pH 5.2). Furthermore, changes in membrane lipid composition, induced either in vitro , by treatment with 25 mM methyl‐β‐cyclodextrin, or in vivo , by subjecting animals to a high‐fat‐diet challenge (60% kcal in fat) reduce autophagosome/lysosome fusion up to 70% of that observed in untreated fractions or from animals under a normal regular diet. These findings reveal a novel role for lipids in autophagic fusion and provide a mechanism for the reduced macroautophagic rates observed during exposure to a chronic lipid challenge. Changes in the intracellular lipid content (i.e., metabolic disorders) may thus have pronounced effects on the fusion step of macroautophagy and affect the overall activity of this intracellular proteolytic pathway.—Koga, H., Kaushik, S., Cuervo, A. M. Altered lipid content inhibits autophagic vesicular fusion. FASEB J . 24, 3052–3065 (2010). www.fasebj.org

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Metadata

Authors
Koga, H., Kaushik, S., & Cuervo, A. M.
Affiliations
Department of Developmental and Molecular Biology Albert Einstein College of Medicine Bronx New York USA
Venue
The FASEB Journal
Publisher
Wiley
Published
2010-04-07
Volume
24
Issue
8
Pages
3052-3065
ISSN
  • 0892-6638
  • 1530-6860
DOI
10.1096/fj.09-144519
Cited by
395
References
4
Language
en
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Funders
  • National Institutes of Health (AG031782, AG021904, DK041918)
  • National Institute on Aging (T32AG023475)

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