Related Experiment Video
Updated: Aug 31, 2025
08:52
Measurement of Protein Turnover Rates in Senescent and Non-Dividing Cultured Cells with Metabolic Labeling and Mass Spectrometry
Published on: April 6, 2022
3.6K
Increasing cell size remodels the proteome and promotes senescence
Michael C Lanz1, Evgeny Zatulovskiy2, Matthew P Swaffer2
1Department of Biology, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, Stanford, CA 94305, USA.
Molecular Cell
|August 20, 2022
Summary
Cell size impacts cell physiology by altering protein concentrations, potentially causing cellular senescence. Increasing cell size without increasing ploidy promotes senescence, highlighting the importance of cell size regulation.
Area of Science:
- Cell Biology
- Molecular Biology
- Physiology
Background:
- Cell size is precisely regulated in healthy tissues.
- The physiological consequences of cell size deviations are not well understood.
Purpose of the Study:
- To investigate how changes in cell size affect the cell's proteome.
- To determine if cell size influences cellular senescence.
Main Methods:
- Quantitative proteomic analysis of cells across a range of sizes.
- Analysis of mRNA concentrations and protein turnover rates.
- Induction of senescence through various methods (replicative, DNA damage, CDK4/6 inhibition).
Main Results:
- Widespread, size-dependent changes in protein concentrations were observed.
- These changes are predictable based on subcellular localization, mRNA levels, and protein turnover.
- Larger proliferating cells exhibit proteomic profiles resembling cellular senescence.
- Increased cell size, particularly without increased ploidy, promotes various forms of senescence.
- Polyploidization prevents size-dependent proteomic changes and senescence.
Conclusions:
- Cell size is a critical regulator of cell physiology through proteome remodeling.
- Large cell size may be a causative factor in cellular senescence.
- Maintaining cell size control and polyploidization are important mechanisms for preventing senescence.
Keywords:
DNA damageSA-beta-Galcell cyclecell sizep16(INK4)palbociclibpolyploidyproteomicssenescencesize-scalingMore Related Videos
Related Concept Videos
02:36Cells Coordinate Growth and Proliferation
4.6K
Cell size is a significant factor impacting cellular design, function, and fitness. There exists some internal coordination by which cells double their masses before division, thus, achieving homeostasis. Coordination between cell growth and proliferation depends on the checkpoints in between cell cycle phases. Loss of coordination or failure in the checkpoint mechanism can drive the cell to uncontrolled growth and loss of cellular function. Like dividing cells that coordinate cellular growth,...
4.6K
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
02:18The Proteasome
8.9K
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
8.9K
01:22Enlargement of the Plasma Membrane
2.0K
Cell division and enlargement are processes that require precise control. The control ensures that cell division cannot proceed unless the cell has grown to a specific size. A spherical, dividing cell requires an approximately 1.6X increase in its surface area to double its volume. The secretory pathway also has a significant role in cell membrane enlargement. Secretory vesicles that bud off from the Golgi apparatus and later fuse with the plasma membrane during exocytosis are a major source of...
2.0K
01:22Cell Size
116.2K
Cell sizes vary widely among and within organisms. Bacterial cells range between 1-10 micrometers (μm)and are considerably smaller than most eukaryotic cells. The smallest bacteria are 0.1 μm in diameter—about a thousand times smaller than eukaryotic cells, which typically range from 10-100 μm.
Surface Area
Cells can take in nutrients and water via diffusion through the plasma membrane itself or through specific channels in the membrane. The area of the membrane surrounding...
Surface Area
Cells can take in nutrients and water via diffusion through the plasma membrane itself or through specific channels in the membrane. The area of the membrane surrounding...
116.2K
01:23Negative Regulator Molecules
35.8K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.8K