Perspective: a stirring role for metabolism in cells

Abstract

Based on recent findings indicating that metabolism might be governed by a limit on the rate at which cells can dissipate Gibbs energy, in this Perspective, we propose a new mechanism of how metabolic activity could globally regulate biomolecular processes in a cell. Specifically, we postulate that Gibbs energy released in metabolic reactions is used to perform work, allowing enzymes to self‐propel or to break free from supramolecular structures. This catalysis‐induced enzyme movement will result in increased intracellular motion, which in turn can compromise biomolecular functions. Once the increased intracellular motion has a detrimental effect on regulatory mechanisms, this will establish a feedback mechanism on metabolic activity, and result in the observed thermodynamic limit. While this proposed explanation for the identified upper rate limit on cellular Gibbs energy dissipation rate awaits experimental validation, it offers an intriguing perspective of how metabolic activity can globally affect biomolecular functions and will hopefully spark new research.

Cellular Allostatic Load is linked to Increased Energy Expenditure and Accelerated Biological Aging

“…This is recapitulated in cells and in patients with primary OxPhos defects, where genetically- or pharmacologically-induced hypermetabolism is associated with accelerated aging and shortened lifespan( 28 ). The damaging nature of hypermetabolism may relate to general constraints on total energy flux imposing limits on molecular operations (i.e., Gibbs free energy dissipation rate)( 103 ), or to intracellular tradeoffs between competing energy-consuming processes( 83 ), although more work is required to understand how such constraints operate in human cells. Further studies are required to establish the directionality and modifiability of this stress-hypermetabolism-aging cascade.…”

Macromolecular Crowding, Phase Separation, and Homeostasis in the Orchestration of Bacterial Cellular Functions

“…Munder and colleagues conclude that acidification and osmotic stress result in different states of the cytoplasm, and thus, the underlying mechanism of reduced diffusion may differ . Altogether, these and other studies − in prokaryotes and eukaryotes show that metabolic activity directly or indirectly affects the apparent viscosity and structural organization of the cytoplasm. Indirect metabolic effects may include stress conditions that affect the stability of the proteome .…”

“…201 It has also been postulated that the dynamics of enzymes catalyzing metabolic reactions can have a "stirring" role in the cytoplasm. 163 Many enzymes are ATP or GTP dependent, and depletion of these nucleotides will reduce the conformational dynamics of these proteins, which indirectly may affect other enzymes. There is debate whether or not enzymes at work (irrespective of ATP) are able to self-propel or to break free from supramolecular structures, 202−204 which would also have a fluidizing effect.…”

“…NMR spectroscopy has shown that ATP interacts weakly with various proteins, which may provide protection to protein surfaces . It has also been postulated that the dynamics of enzymes catalyzing metabolic reactions can have a “stirring” role in the cytoplasm . Many enzymes are ATP or GTP dependent, and depletion of these nucleotides will reduce the conformational dynamics of these proteins, which indirectly may affect other enzymes.…”

Reprogramming a high robustGeobacillus thermoglucosidasiusfor efficient synthesis of polymer-grade lactic acid under extremely high temperature (60°C)

“…These advantages contribute to the reduction in production costs. In addition, it can make unfavorable reactions thermodynamically feasible in mesophilic microorganisms 31 . It can provide fermentation media with good properties, such as lower viscosity, faster substrate diffusion rates, and better substrate solubility 20 .…”