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Related Concept Videos

Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
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Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
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The Proteasome01:13

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Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy
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Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy

Published on: January 31, 2025

Autophagy takes an alternative pathway.

Shigeomi Shimizu1, Satoko Arakawa, Yuya Nishida

  • 1Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan. shimizu.pcb@mri.tmd.ac.jp

Autophagy
|January 28, 2010
PubMed
Summary

Mammalian cells possess two macroautophagy pathways. An alternative pathway exists that does not require ATG5 or ATG7 proteins, functioning independently of conventional autophagy markers like LC3 lipidation.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Autophagy Research

Background:

  • ATG5 and ATG7 proteins are traditionally viewed as essential for initiating macroautophagy.
  • LC3 lipidation is a widely accepted marker for monitoring macroautophagy.
  • The precise mechanisms governing all forms of cellular autophagy are not fully elucidated.

Purpose of the Study:

  • To investigate the existence and characteristics of ATG5/ATG7-independent macroautophagy.
  • To determine if alternative autophagy pathways exist in mammalian cells.
  • To characterize the molecular machinery involved in ATG5/ATG7-independent autophagy.

Main Methods:

  • Utilizing cell lines deficient in ATG5 or ATG7.
  • Inducing cellular stress to trigger autophagy.
  • Analyzing autophagosome and autolysosome formation and function.
  • Investigating LC3 lipidation status.
  • Employing Rab9 dependency assays and vesicle trafficking studies.

Main Results:

  • Cells lacking ATG5 or ATG7 can still execute autophagy-mediated protein degradation and form autophagosomes/autolysosomes under specific stress conditions.
  • LC3 lipidation, a hallmark of conventional macroautophagy, was absent in this ATG5/ATG7-independent process.
  • Autophagosome biogenesis appeared to involve Rab9-dependent fusion with vesicles originating from the trans-Golgi network and late endosomes.
  • This suggests an alternative pathway for macroautophagy distinct from the conventional ATG5/ATG7-dependent route.

Conclusions:

  • Mammalian macroautophagy can proceed through at least two distinct pathways.
  • An ATG5/ATG7-dependent conventional pathway exists.
  • An ATG5/ATG7-independent alternative pathway operates, utilizing different molecular mechanisms for autophagosome formation and function.