Metabo-reciprocity in cell mechanics: feeling the demands/feeding the demand

Dysregulated cell metabolism and a corrupted mechanical environment promote the progression of fibrotic diseases. Recent evidence suggests that mechanical stimuli and dysregulated cell metabolism act as two integrally related molecular drivers of fibrotic diseases. Mechanical forces rewire the metabolism of mechano-activated cells to sustain their metabolic needs. Metabolic inputs reprogram cell mechanics to adapt cells to their mechanically constrained environment. Targeting the mechano-metabolic axis can attenuate fibrotic disease progression. Altered metabolic programs and corruption of tissue architecture are hallmarks of disease. The spatiotemporal control of cell behavior requires transmission of information from the complex structure of tissues to their constituent cells. Cytoskeletal mechanotransduction enables this transmission by sensing mechanical environments and adapting cellular behaviors. However, this process requires energy. Recent findings have shed light on the bidirectional relationship between mechanical forces and upstream and downstream metabolic cues. We discuss recent advances in the reciprocal regulation ('metabo-reciprocity') that allows cells to adapt their metabolic needs to their mechanically constrained environment but can also contribute to adjustable feedback that promotes disease progression. Altered metabolic programs and corruption of tissue architecture are hallmarks of disease. The spatiotemporal control of cell behavior requires transmission of information from the complex structure of tissues to their constituent cells. Cytoskeletal mechanotransduction enables this transmission by sensing mechanical environments and adapting cellular behaviors. However, this process requires energy. Recent findings have shed light on the bidirectional relationship between mechanical forces and upstream and downstream metabolic cues. We discuss recent advances in the reciprocal regulation ('metabo-reciprocity') that allows cells to adapt their metabolic needs to their mechanically constrained environment but can also contribute to adjustable feedback that promotes disease progression. the main cellular energy currency. In mammalian cells, ATP is produced by oxidative respiration or glycolysis. In addition to being used as an energy source, it is also used in signal transduction pathways and is incorporated into RNA during RNA synthesis. the process of formation of intermediates of metabolic pathways such as the TCA cycle. Indeed, the intermediaries of the metabolic cycles are finely regulated to maintain a dynamic state of equilibrium. The main anaplerotic substrates are pyruvate and glutamine/glutamate. a series of chemical reactions that convert glutamine to α-ketoglutarate to replenish the TCA cycle. a post-translational modification (PTM) that consists of adding a variable number of glutamate residues as a secondary branch to the main protein sequence. Although discovered on tubulin, diverse proteins have been shown to be glutamylated. Glutamylation can modify protein localization, interaction, activity, or stability. a cytosolic series of chemical reactions that break down a molecule of glucose into two molecules of pyruvate and produce ATP. a PTM that has been mainly described as a tubulin modification. It consists of adding a variable number of glycine residues as a secondary branch to the main protein sequence. an evolutionarily conserved pathway that controls organ size by regulating cell proliferation, apoptosis, and differentiation. It consists of a cascade of phosphorylation events mediated by two protein kinase families – MST1/MST2 and LATS1/LATS2 – which phosphorylate the YAP and TAZ proteins, thus controlling their nucleocytoplasmic shuttling and their activities as transcriptional coactivators. the energy-producing pathway in which the electrochemical gradient generated across the inner mitochondrial membrane by the respiratory chain complexes is used to generate ATP. key components of cell membranes. Phospholipids are a class of lipids with a hydrophilic 'head' containing a phosphate group, and two hydrophobic tails derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). a series of chemical reactions taking place in mitochondria that generate energy through the oxidation of acetyl-CoA provided by the degradation of glucose, fatty acids, or amino acids. In addition, the TCA cycle provides precursors for the biosynthesis of macromolecules.