Excessive Cell Growth Causes Cytoplasm Dilution And Contributes to Senescence

Neurohr, Gabriel E.; Terry, Rachel; Lengefeld, Jette; Bonney, Megan; Brittingham, Gregory; Moretto, Fabien; Miettinen, Teemu P.; Vaites, Laura Pontano; Soares, Luis M.; Paulo, João A.; Harper, J. Wade; Buratowski, Stephen; Manalis, Scott R.; Werven, Folkert J. van; Holt, Liam J.; Amon, Angelika

doi:10.1016/j.cell.2019.01.018

Cited by 402 publications

(590 citation statements)

References 54 publications

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“…Persistent mTORC1 activation and cell mass accumulation in cell cycle-arrested cells have been suggested to lead to senescence induction 74 and to contribute to the functional decline in senescent cells. 75 AMPK has also been suggested to play a role in the induction of senescence with temporarily restricted AMPK induction allowing adaptation to stress and persistent AMPK activation leading the cells toward irreversible senescence. 76 This prompts the question: What is the role of these metabolic checkpoints in B lymphoma development and propagation?…”

Section: Epstein-barr Virus (Ebv) Has Been Shown To Results In An Initialmentioning

confidence: 99%

The role of metabolic checkpoint regulators in B cell survival and transformation

Jellusova

2020

Immunological Reviews

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In response to mitogenic stimulation, B cells activate different pro-anabolic signaling pathways such as c-Myc-and mTORC1-dependent networks to satisfy the energetic demands of biomass synthesis and proliferation. In order to preserve viability and function, cell growth cannot progress unchecked and must be adjusted according to the availability of nutrients. Nutrient-sensing proteins such as AMPK antagonize mTORC1 activity in response to starvation. If pro-anabolic signaling pathways are aberrantly activated, B cells may lack the metabolic capacity to accommodate their energetic needs, which can lead to cell death. On the other hand, metabolic hyperactivation is a salient feature of cancer cells, suggesting that mechanisms exist, which allow B cells to cope with metabolic stress. The aim of this review is to discuss how B cells respond to a mismatch between energy supply and demand and what the consequences are of metabolic dysregulation in normal and malignant B cells. K E Y W O R D Sanabolism, autophagy, B cells, metabolic stress, mTORC1, senescence

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Section: Epstein-barr Virus (Ebv) Has Been Shown To Results In An Initialmentioning

confidence: 99%

The role of metabolic checkpoint regulators in B cell survival and transformation

Jellusova

2020

Immunological Reviews

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“…In any analysis cell size can be reported either as cell volume or as cell mass. Cell volume and cell mass are generally tightly correlated, but changes in volume can be transient and are also known to occur during different stages of differentiation or the cell cycle (9)(10)(11)(12). By contrast, cell mass or cell protein mass, which is the sum of slower anabolic and degradative processes, is generally more closely related to the regulation of growth rate.…”

Section: Introductionmentioning

confidence: 99%

Computationally Enhanced Quantitative Phase Microscopy Reveals Autonomous Oscillations in Mammalian Cell Growth

Liu

Peshkin

et al. 2019

Preprint

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The regulation of growth is fundamental to cell size control. Lack of sufficient accuracy in the measurement of the growth rate of adherent cells through the cell cycle has thwarted the understanding of how such cell populations maintain a stable size distribution. The accuracy of Quantitative Phase Microscopy (QPM) is just shy of the accuracy needed to resolve the principle features of mammalian cell growth and perhaps to reveal new ones. Based on our analysis of the source of errors in QPM we both improved image processing algorithms and automated cell tracking software, making it suitable for longitudinal and large scale applications. Using these tools we revealed a remarkable a series of episodes of the convergence of cell growth rate, which may play a large role in the control of cell size variability.Main text

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“…Keeping cell size homeostasis during proliferation is crucial for maintaining optimal cell physiology, and may be important for proper tissue geometry and function [26][27][28][29][30][31]. One way that cell size can be controlled is by coupling cell cycle progression to cell growth through a sizer, in which growth over a single cycle compensates for variation in birth size.…”

Section: Discussionmentioning

confidence: 99%

A G1 sizer mechanism coordinates growth and division in the mouse epidermis

Xie

2019

Preprint

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Cell size homeostasis is often achieved by coupling cell cycle progression to cell growth. Studies of cell size homeostasis in single-celled bacteria and yeast have observed several distinct phenomena. Growth can be coupled to division through a range of mechanisms, including a 'sizer', wherein cells of varying birth size divide at similar final sizes [1-3], and an 'adder', wherein cells increase in size a fixed amount per cell cycle [4][5][6]. Importantly, intermediate control mechanisms are observed, and even the same organism can exhibit distinct control phenomena depending on growth conditions [2,7,8]. While studying unicellular organisms in laboratory conditions may give insight into their growth control in the wild, this is less apparent for studies of mammalian cells growing outside the organism. Sizer, adder, and intermediate mechanisms have been observed in vitro [9-12], but it is unclear how these diverse size homeostasis phenomena relate to mammalian cell proliferation in vivo. To address this gap, we analyzed time-lapse images of the mouse epidermis taken over one week during normal tissue turnover [13]. We quantified the 3D volume growth and cell cycle progression of single cells within the mouse skin. In dividing epidermal stem cells, we found that cell growth is coupled to division through a sizer mechanism operating largely in the G1 phase. Thus, while the majority of tissue culture studies to-date identified adder mechanisms, our analysis demonstrates that sizer mechanisms are important in vivo and highlights the need to determine their underlying molecular origin.

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Excessive Cell Growth Causes Cytoplasm Dilution And Contributes to Senescence

Cited by 402 publications

References 54 publications

The role of metabolic checkpoint regulators in B cell survival and transformation

The role of metabolic checkpoint regulators in B cell survival and transformation

Computationally Enhanced Quantitative Phase Microscopy Reveals Autonomous Oscillations in Mammalian Cell Growth

A G1 sizer mechanism coordinates growth and division in the mouse epidermis

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