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Related Concept Videos

Lysosomal Hydrolases01:22

Lysosomal Hydrolases

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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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pH Regulation in Cells01:28

pH Regulation in Cells

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pH plays a critical role in maintaining normal cellular activities. It helps maintain the structure and function of various proteins, dictates the charge on cellular membranes, and is crucial for metabolic reactions inside the cell. Moreover, cells use the energy from the proton motive force to generate ATP.
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
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Lysosomes01:31

Lysosomes

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Lysosomes are membrane-enclosed spherical sacs derived from the Golgi apparatus. The most important function of the lysosome is degrading macromolecules and biological polymers that are released during membrane trafficking events such as the secretory, endocytic, autophagic, and phagocytic pathways. The degradation is carried out by several hydrolytic enzymes active in an acidic environment of the lysosomal lumen. These acid hydrolases are involved in cellular processes such as cell signaling,...
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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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Maturation of Endosomes01:28

Maturation of Endosomes

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The early endosome containing internalized molecules matures through transformations in its location, morphology, intraluminal pH, and membrane protein composition. Together, these changes result in a more acidic late endosome that contains multiple intraluminal vesicles; therefore, the late endosome is also called a multivesicular body (MVB).
Changes in location
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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.
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Assessing Lysosomal Alkalinization in the Intestine of Live Caenorhabditis elegans
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Extracellular Acidification Induces Lysosomal Dysregulation.

Bryce Ordway1, Robert J Gillies1, Mehdi Damaghi1,2

  • 1Department of Cancer Physiology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.

Cells
|June 2, 2021
PubMed
Summary

Cancer cells face harsh tumor microenvironments, including acidosis. Acid stress disrupts lysosomal function, potentially driving cancer evolution and offering therapeutic targets.

Keywords:
Warburg effectbreast cancercancer acidosiscancer metastasisintracellular pHlysosomal localizationlysosome dysregulationtargeted therapytumor microenvironment

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Area of Science:

  • Oncology
  • Cancer Biology
  • Cellular Stress Response

Background:

  • Invasive cancers develop over years via somatic evolution, accumulating genetic/epigenetic changes and aggressive clones.
  • Solid tumors like breast ductal carcinoma present harsh extracellular environments, including hypoxia, nutrient deprivation, and inflammation.
  • Acidosis, caused by the Warburg effect (lactic acid fermentation), is a constant stressor for cancer cells.

Purpose of the Study:

  • To investigate the impact of acid stress on lysosomal function in cancer cells.
  • To explore the mechanisms underlying lysosomal dysregulation under prolonged acid exposure.
  • To identify potential therapeutic opportunities arising from understanding acid stress-induced lysosomal dysfunction.

Main Methods:

  • The study likely involves exposing cancer cells (e.g., breast ductal carcinoma models) to acidic conditions mimicking tumor microenvironments.
  • Analysis of lysosomal function, including morphology, enzyme activity, and membrane integrity, under varying durations of acid stress.
  • Investigation into potential epigenetic modifications or evolutionary selection pressures contributing to lysosomal dysregulation.

Main Results:

  • Short-term acid stress significantly affects lysosomal function in exposed cells.
  • Long-term exposure to acidic conditions leads to complete dysregulation of lysosomal function in cancer cells.
  • The precise mechanisms (epigenetic change vs. evolutionary selection) driving this dysregulation require further elucidation.

Conclusions:

  • Acid stress is a critical factor impacting cancer cell biology, particularly lysosomal function.
  • Dysregulated lysosomal function due to acidosis may contribute to cancer progression and aggressiveness.
  • Understanding these mechanisms could reveal novel therapeutic strategies targeting cancer's response to acidic tumor microenvironments.