Localized Glucose Import, Glycolytic Processing, and Mitochondria Generate a Focused ATP Burst to Power Basement Membrane Invasion

Atossa : a royal link between OXPHOS metabolism and macrophage migration

“…Anchor cells may create a cellular microenvironment enriched with glucose receptors, glycolytic enzymes and mitochondria that would energetically support the migration at the tip of the protrusions, which appears to align with the results reported by Emtenani et al (2022). These findings might reconcile the duality between glycolysis (Guak & Krawczyk, 2020) and OXPHOS (Emtenani et al, 2022;Garde et al, 2022) dependency during invasion indicating that cells undergo spatially focalized metabolic switches within the same cell to promote invasion and migration. While further studies in mammals need to validate the implications and dynamics of Atossa in controlling immune or other tissue responses under energetic demands, these studies identify a regulatory process orchestrated from the nucleus between mitochondrial bioenergetics and macrophage function.…”

“…A recent work in C . elegans shows that anchor cell invasion requires bursts of localized mitochondrial generated‐ATP to promote cell migration through the tissues (Garde et al , 2022). Anchor cells may create an cellular microenvironment enriched with glucose receptors, glycolytic enzymes and mitochondria that would energetically support the migration at the tip of the protrusions, which appears to align with the results reported by Emtenani et al (2022).…”

Parallel Activation of Src and Hif1α Increases Localized Glycolytic ATP Generation for Re-assembly of Endothelial Adherens Junctions

“…Recent studies are identifying the critical role of compartmentalized metabolic shifts in the regulation of cellular junction homeostasis and integrity such as the observation that the glucose transporter Glut1 is recruited to junction sites to meet the energy requirements of cytoskeleton remodeling responses to shear stress (Salvi, Bays et al 2021). Localized expression of the glucose transporter in the front end of invasive cells provides ATP burst to breach basement membrane barrier (Garde, Kenny et al 2022). In this study we show that PFKFB3, a glycolysis regulatory enzyme that is downstream of the Glut1 transporter, is required for reassembly of adherens junction and that post-translational modification of this essential metabolic enzyme is a means by which restoration of cellular barrier integrity can be controlled.…”

“…One devastating example of excessive fluid leak due to downregulation of AJs can be seen in the inflammatory lung injury during sepsis or severe SARS-CoV-2 infection. Inflammation-mediated AJs disruption leads to excessive neutrophil infiltration and protein-rich fluid leak into lung air space, resulting in edema and respiratory failure (Matthay, Zemans et al 2019, Garde, Kenny et al 2022, Zhang, Dutta et al 2022). Thus, restoring the integrity of the endothelial barrier is a central factor determining the degree and extent of recovery (Zhang, Li et al 2019, Evans, Iruela-Arispe et al 2021).…”

A light sheet fluorescence microscopy protocol for Caenorhabditis elegans larvae and adults

“…C. elegans is also amenable to high-resolution live imaging of genetically encoded fluorophores fused to proteins to follow protein dynamics and assess gene expression levels and patterns (Keeley et al 2020; Heppert et al 2018; Tsuyama et al 2013; Yoshida et al 2017; Mita et al 2019). Genetically encoded fluorophores can also be conjugated to biosensors, which have been used to quantitatively monitor cell cycle state (Adikes et al 2020) and ATP in C. elegans larvae (Garde et al 2022). C. elegans can also be easily stained with vital dyes (Kelley et al 2019; Schultz and Gumienny 2012; Hermann et al 2005).…”