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Related Concept Videos

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.
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In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
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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.
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Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
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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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Lysosomal Hydrolases01:22

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Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
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Feedback Regulation of Calcium Concentration01:27

Feedback Regulation of Calcium Concentration

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Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
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Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

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Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
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Related Experiment Video

Updated: Apr 12, 2026

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

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Lysosomal calcium regulates autophagy.

Diego L Medina1, Andrea Ballabio

  • 1a Telethon Institute of Genetics and Medicine (TIGEM) ; Pozzuoli, Naples , Italy.

Autophagy
|May 23, 2015
PubMed
Summary

The lysosome signals nutrient levels by releasing calcium, activating the master autophagy regulator TFEB (transcription factor EB) through calcineurin. This discovery highlights the lysosome's role in cellular homeostasis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Autophagy Research

Background:

  • The lysosome is increasingly recognized as a central signaling hub in cellular processes.
  • Nutrient availability is a key environmental cue that cells must sense to maintain homeostasis.
  • Autophagy, a crucial degradation pathway, is tightly regulated by cellular signaling networks.

Purpose of the Study:

  • To investigate the role of lysosomal calcium signaling in cellular homeostasis.
  • To identify novel mechanisms by which the lysosome regulates autophagy.
  • To elucidate the signaling pathway linking lysosomal calcium release to the master autophagy regulator TFEB.

Main Methods:

  • Utilized cell-based assays to monitor lysosomal calcium dynamics.
  • Employed biochemical techniques to study protein-protein interactions.
Keywords:
TFEBTRPML1autophagycalcineurinlysosomal calcium

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  • Investigated the activation of TFEB (transcription factor EB) in response to lysosomal stimuli.

    • Main Results:

    • Demonstrated that lysosomal calcium release is a key event in nutrient sensing.
    • Showed that calcineurin acts as a direct link between lysosomal calcium and TFEB activation.
    • Confirmed that this pathway is essential for adaptive cellular responses.

    Conclusions:

    • Lysosomal calcium release is a novel signaling mechanism.
    • This pathway represents a critical node for integrating nutrient status with autophagy regulation.
    • The lysosome's role as a signaling organelle is further expanded by this finding.