Related Experiment Video
Updated: Aug 5, 2025
06:18
Assessing Lysosomal Alkalinization in the Intestine of Live Caenorhabditis elegans
Published on: April 13, 2018
6.0K
TFEB-dependent lysosome biogenesis is required for senescence.
Rachel Curnock1, Katy Yalci1, Johan Palmfeldt2
1School of Biochemistry, University of Bristol, Bristol, UK.
The EMBO Journal
|March 27, 2023
Summary
Cellular senescence drives ageing, characterized by increased lysosomes. This study reveals senescent cell lysosomes are dysfunctional but TFEB/TFE3 activation maintains cellular function, proving crucial for senescent cell survival.
Area of Science:
- Cellular Biology
- Aging Research
- Lysosome Biology
Background:
- Cellular senescence is a key driver of organismal aging.
- Lysosomal dysfunction is a hallmark of senescent cells, impacting cell metabolism.
- The specific role of lysosome biogenesis in senescence remains unclear.
Purpose of the Study:
- To investigate the cause and consequences of lysosome biogenesis in cellular senescence.
- To determine the role of TFEB/TFE3 transcription factors in lysosomal changes during senescence.
- To understand the impact of lysosomal alterations on senescent cell survival and function.
Main Methods:
- Senescence induction and characterization.
- Lysosomal function assays (pH, membrane integrity, proteolytic capacity).
- Analysis of TFEB/TFE3 localization and phosphorylation.
- Genetic manipulation of TFEB/TFE3 in senescent cells.
Main Results:
- Senescent cells exhibit dysfunctional lysosomes (higher pH, membrane damage, reduced proteolysis).
- Despite dysfunction, increased lysosomal content maintains cellular degradative capacity.
- Nuclear TFEB/TFE3 activation is a hallmark of senescence, supporting lysosome biogenesis and senescent cell survival.
- TFEB/TFE3 are hypo-phosphorylated and constitutively nuclear in senescent cells.
Conclusions:
- Lysosome biogenesis, driven by nuclear TFEB/TFE3, is essential for senescent cell survival despite lysosomal dysfunction.
- Dysregulation of TFEB/TFE3 pathways contributes to senescence.
- Targeting TFEB/TFE3 may offer therapeutic strategies for age-related diseases.
More Related Videos
Related Concept Videos
01:36Delivery Pathways to the Lysosome
6.6K
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...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
6.6K
02:15Replicative Cell Senescence
3.7K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.7K
01:22Lysosomal Hydrolases
3.9K
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,...
3.9K
01:28Maturation of Endosomes
4.3K
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
The maturing endosome moves along microtubules from the periphery of the cell towards the perinuclear region. This movement of the...
Changes in location
The maturing endosome moves along microtubules from the periphery of the cell towards the perinuclear region. This movement of the...
4.3K
01:38Intralumenal Vesicles and Multivesicular Bodies
3.6K
Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
3.6K
01:27Autophagy
4.4K
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,...
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.4K