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Related Concept Videos

Autophagy01:27

Autophagy

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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.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
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Autophagic Cell Death01:18

Autophagic Cell Death

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Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
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Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

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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.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
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Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

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Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized...
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Nuclear Export of mRNA02:31

Nuclear Export of mRNA

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Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
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Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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Related Experiment Video

Updated: Jun 4, 2025

In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice
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In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice

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Macronucleophagy maintains cell viability under nitrogen starvation by modulating micronucleophagy.

Ziyang Li1,2, Keisuke Mochida1,2, Hitoshi Nakatogawa3,4

  • 1Cell Biology Center, Institute of Integrated Research, Institute of Science Tokyo, Yokohama, Japan.

Nature Communications
|December 17, 2024
PubMed
Summary

Autophagy, a cellular process, involves two main pathways: macroautophagy and microautophagy. In yeast, impaired macroautophagy (Atg39-mediated) leads to overactive microautophagy, causing excessive nuclear degradation and cell death during starvation.

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A Fluorescence Microscopy Assay for Monitoring Mitophagy in the Yeast Saccharomyces cerevisiae
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A Fluorescence Microscopy Assay for Monitoring Mitophagy in the Yeast Saccharomyces cerevisiae

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Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome
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Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome
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Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Yeast Genetics

Background:

  • Autophagy is essential for cellular homeostasis, involving lysosome/vacuole-mediated degradation.
  • Nitrogen starvation in Saccharomyces cerevisiae induces both macronucleophagy and micronucleophagy.
  • The interplay between different autophagy modes, particularly concerning nuclear degradation, remains poorly understood.

Purpose of the Study:

  • To elucidate the mechanism by which Atg39-mediated macronucleophagy influences micronucleophagy.
  • To investigate the relationship between macronucleophagy and micronucleophagy under nitrogen starvation.
  • To understand how disruptions in macronucleophagy affect nuclear component degradation and cell survival.

Main Methods:

  • Genetic analysis of Saccharomyces cerevisiae mutants with defects in Atg39-mediated macronucleophagy.
  • Microscopy and biochemical assays to monitor nuclear component transport into the vacuole.
  • Analysis of protein localization and degradation at the nucleus-vacuole junction (NVJ).

Main Results:

  • Defective Atg39-mediated macronucleophagy leads to hyperactivated micronucleophagy.
  • Accumulation of the micronucleophagy component Nvj1 in macronucleophagy-deficient cells.
  • Blocking micronucleophagy rescues cell death in Atg39-mutant cells under nitrogen starvation.

Conclusions:

  • Macronucleophagy acts as a negative regulator of micronucleophagy to prevent excessive nuclear degradation.
  • The Atg39-mediated pathway is crucial for maintaining nuclear and cellular homeostasis during nutrient stress.
  • Dysregulation of the balance between macroautophagy and microautophagy can lead to cell death.