Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation

Petrovska, Ivana; Nüske, Elisabeth; Munder, Matthias C.; Kulasegaran, Gayathrie; Gibson, Kimberley; Malinovska, Liliana; Richter, Doris; Verbavatz, Jean‐Marc; Alberti, Simon

doi:10.1101/003277

Cited by 98 publications

(211 citation statements)

References 55 publications

Supporting

Mentioning

198

Contrasting

Order By: Relevance

“…14,163 On the other hand, it is also important to note here that metabolic enzyme complexes have been formed to play as intracellular depot systems, demonstrating that the formation of metabolic complex is not the direct indication of metabolic flux enhancement. 164 Various spatial assemblies are also formed by single enzymes or only a subset of enzymes of given pathways, further indicating potential functional diversities of spatial metabolic assemblies in cells beyond flux enhancement. 35,100,119 It is clear that there is still much to be learned about biological significance of the compartmentalization of metabolic enzymes in cells.…”

Section: Discussionmentioning

confidence: 99%

Spatial Organization of Metabolic Enzyme Complexes in Cells

2017

View full text Add to dashboard Cite

The organization of metabolic multienzyme complexes has been hypothesized to benefit metabolic processes and provide a coordinated way for the cell to regulate metabolism. Historically, their existence has been supported by various in vitro techniques. However, it is only recently that the existence of metabolic complexes inside living cells has come to light to corroborate this long-standing hypothesis. Indeed, subcellular compartmentalization of metabolic enzymes appears to be widespread and highly regulated. On the other hand, it is still challenging to demonstrate the functional significance of these enzyme complexes in the context of the cellular milieu. In this review, we discuss the current understanding of metabolic enzyme complexes by primarily focusing on central carbon metabolism and closely associated metabolic pathways in a variety of organisms, as well as their regulation and functional contributions to cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Spatial Organization of Metabolic Enzyme Complexes in Cells

2017

View full text Add to dashboard Cite

show abstract

“…In yeast, nutrient starvation can induce ~20% of cytosolic metabolic enzymes to reorganize into reversible assemblies 65 . One of these enzymes, glutamine synthetase, does so in response to a drop in cytosolic pH caused by the nutrient depletion, thereby attenuating nitrogen metabolism in response to starvation 65,66 . Similarly, yeast pyruvate kinase forms amyloid-like solid aggregates in response to glucose starvation 67 .…”

Section: Regulating Phase Separationmentioning

confidence: 99%

It Pays To Be in Phase

2018

View full text Add to dashboard Cite

To survive, organisms must orchestrate many competing biochemical and regulatory processes in time and space. Recent work has suggested that the underlying chemical properties of some biomolecules allow them to self-organize, and that life may have exploited this property to organize biochemistry in space and time within cells. Such phase separation is ubiquitous, particularly among the many regulatory proteins that harbor prion-like intrinsically disordered domains. And yet, despite evident regulation by post-translational modification and myriad other stimuli, the biological significance of many phase-separated compartments remains uncertain. Many potential functions have been proposed but far fewer have been demonstrated. A burgeoning subfield at the intersection of cell biology and polymer physics has defined the biophysical underpinnings that govern the genesis and stability of these particles. The picture is complex: many assemblies are composed of multiple proteins that each have the capacity to phase separate. Here, we briefly discuss this foundational work and survey recent efforts combining targeted biochemical perturbations and quantitative modeling to specifically address the diverse roles that phase separation processes may play in biology.

show abstract

“…Interestingly, phase separation has been achieved in vitro using reconstituted or even designed components [137]. While this protein-rich phase is liquid-like, other proteins can form crystalline assemblies; and macromolecular crowding can drive their formation [138]. Modeling such as that enabled by FMAP (Qin and Zhou, submitted) and other techniques and in vitro experiments mimicking cellular conditions will allow us to reach quantitative understanding of all these emergent behaviors in the cellular context.…”

Section: Atomistic Modeling Of Thermodynamic and Kinetic Effects Of Cmentioning

confidence: 99%

Challenges in structural approaches to cell modeling

Liang

Olson

et al. 2016

Journal of Molecular Biology

View full text Add to dashboard Cite

Computational modeling is essential for structural characterization of biomolecular mechanisms across the broad spectrum of scales. Adequate understanding of biomolecular mechanisms inherently involves our ability to model them. Structural modeling of individual biomolecules and their interactions has been rapidly progressing. However, in terms of the broader picture, the focus is shifting toward larger systems, up to the level of a cell. Such modeling involves a more dynamic and realistic representation of the interactomes in vivo, in a crowded cellular environment, as well as membranes and membrane proteins, and other cellular components. Structural modeling of a cell complements computational approaches to cellular mechanisms based on differential equations, graph models, and other techniques to model biological networks, imaging data, etc. Structural modeling along with other computational and experimental approaches will provide a fundamental understanding of life at the molecular level and lead to important applications to biology and medicine. A cross section of diverse approaches presented in this review illustrates the developing shift from the structural modeling of individual molecules to that of cell biology. Studies in several related areas are covered: biological networks; automated construction of three-dimensional cell models using experimental data; modeling of protein complexes; prediction of non-specific and transient protein interactions; thermodynamic and kinetic effects of crowding; cellular membrane modeling; and modeling of chromosomes. The review presents an expert opinion on the current state-of-the-art in these various aspects of structural modeling in cellular biology, and the prospects of future developments in this emerging field.

show abstract

Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation

Cited by 98 publications

References 55 publications

Spatial Organization of Metabolic Enzyme Complexes in Cells

Spatial Organization of Metabolic Enzyme Complexes in Cells

It Pays To Be in Phase

Challenges in structural approaches to cell modeling

Contact Info

Product

Resources

About