Regulation with cell size ensures mitochondrial DNA homeostasis during cell growth

Seel, Anika; Padovani, Francesco; Finster, Alissa; Mayer, Moritz; Bureik, Daniela; Osman, Christof; Klecker, Till; Schmoller, Kurt M.

doi:10.1101/2021.12.03.471050

Cited by 7 publications

(5 citation statements)

References 66 publications

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“…In heterotrophic organisms, the increase in overall mitochondrial volume accompanying increased cell volume is primarily accomplished through an increase in mitochondrial number rather than size (Okie et al 2016). In addition, experimental manipulations in yeast demonstrate that mitochondrial shape stays the same across increasing cell and overall mitochondrial volumes (Seel et al 2022). Our results showing unchanged mitochondrial SA:V ratio across our model amphibians also suggest isometric growth of the total mitochondrial network with respect to its shape, consistent with these previous results.…”

Section: Scaling Of the Mitochondriasupporting

confidence: 92%

Gigantic animal cells suggest organellar scaling mechanisms across a 50-fold range in cell volume

Adams,

Smith,

Raad

et al. 2023

Evolution

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The largest cells are orders of magnitude bigger than the smallest cells. Organelle content scales to maintain cell function, with different organelles increasing in volume, length, or number as cells increase in size. Scaling may also reflect functional demands placed on organelles by increased cell size. Amphibians exhibit exceptional diversity in cell size. Using transmission electron microscopy, we analyzed three species whose enterocyte cell volumes range from 228 to 10,593 μm3. We show that nuclear volume increases by an increase in radius while mitochondrial volume increases by an increase in total network length; the endoplasmic reticulum and Golgi apparatus, with their complex shapes, are intermediate. Notably, all four organelle types increase in total volume proportional to cell volume, despite variation in functional (i.e. metabolic, transport) demands. This pattern suggests that organellar building blocks are incorporated into more or larger organelles following the same rules across species that vary ~50-fold in cell sizes, consistent with a “limited precursor” model for organellar scaling that, in turn, assumes equivalent cytoplasmic concentrations of organellar building block proteins. Taken together, our results lead us to hypothesize that salamanders have evolved increased biosynthetic capacity to maintain functional protein concentrations despite huge cell volumes.

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Section: Scaling Of the Mitochondriasupporting

confidence: 92%

Gigantic animal cells suggest organellar scaling mechanisms across a 50-fold range in cell volume

Adams,

Smith,

Raad

et al. 2023

Evolution

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“…Mitochondrial volume typically scales with cell size in dividing cells supporting faithful cellular functions ( Posakony et al, 1977 ; Rafelski et al, 2012 ; Miettinen and Bjorklund, 2016 ; Cheng et al, 2021 ; Lanz et al, 2021 ; Seel et al, 2022 ). For example, HSCs are able to scale mitochondria upon their activation ( Ho et al, 2017 ).…”

Section: Interplay Between Cellular Enlargement Of Hematopoietic Stem...mentioning

confidence: 99%

Cellular enlargement - A new hallmark of aging?

Davies

Handel

Bharadwaj

et al. 2022

Front. Cell Dev. Biol.

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Years of important research has revealed that cells heavily invest in regulating their size. Nevertheless, it has remained unclear why accurate size control is so important. Our recent study using hematopoietic stem cells (HSCs) in vivo indicates that cellular enlargement is causally associated with aging. Here, we present an overview of these findings and their implications. Furthermore, we performed a broad literature analysis to evaluate the potential of cellular enlargement as a new aging hallmark and to examine its connection to previously described aging hallmarks. Finally, we highlight interesting work presenting a correlation between cell size and age-related diseases. Taken together, we found mounting evidence linking cellular enlargement to aging and age-related diseases. Therefore, we encourage researchers from seemingly unrelated areas to take a fresh look at their data from the perspective of cell size.

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“…Mitochondrial content increases with respect to cell size [80][81][82]. Indeed, mitochondrial DNA content has been shown to scale with cell volume rather than nuclear genome content in yeast [83,84], demonstrating an intrinsic relationship between cell size and mitochondrial abundance. Still, the scaling of mitochondrial content does not guarantee mitochondrial function.…”

Section: Mitochondrial Dysfunction In Enlarged Cellsmentioning

confidence: 99%

Too big not to fail: emerging evidence for size‐induced senescence

Manohar,

Neurohr

2023

The FEBS Journal

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Cellular senescence refers to a permanent and stable state of cell cycle exit. This process plays an important role in many cellular functions, including tumor suppression. It was first noted that senescence is associated with increased cell size in the early 1960s; however, how this contributes to permanent cell cycle exit was poorly understood until recently. In this review, we discuss new findings that identify increased cell size as not only a consequence but also a cause of permanent cell cycle exit. We highlight recent insights into how increased cell size alters normal cellular physiology and creates homeostatic imbalances that contribute to senescence induction. Finally, we focus on the potential clinical implications of these findings in the context of cell cycle arrest‐causing cancer therapeutics and speculate on how tumor cell size changes may impact outcomes in patients treated with these drugs.

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Regulation with cell size ensures mitochondrial DNA homeostasis during cell growth

Cited by 7 publications

References 66 publications

Gigantic animal cells suggest organellar scaling mechanisms across a 50-fold range in cell volume

Gigantic animal cells suggest organellar scaling mechanisms across a 50-fold range in cell volume

Cellular enlargement - A new hallmark of aging?

Too big not to fail: emerging evidence for size‐induced senescence

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