Localized glucose import, glycolytic processing, and mitochondria generate a focused ATP burst to power basement-membrane invasion

Garde, Aastha; Kenny, Isabel W.; Kelley, Laura C.; Chi, Qiuyi; Mutlu, Ayse Sena; Wang, Meng C.; Sherwood, David R.

doi:10.1016/j.devcel.2022.02.019

Cited by 30 publications

(40 citation statements)

References 91 publications

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“…Mitochondria also respond to increased levels of extracellular glucose, where O-GlcNAc transferase (OGT) performs the glucose-dependent O-GlcNAcylation on key serine residues of the adaptor protein Milton which stops mitochondrial motility (Pekkurnaz et al, 2014). Similarly, by inhibiting the glucose transporter FGT-1 in Caenorhabditis elegans, there was a decreased mitochondrial recruitment to the basal membrane to help drive anchor cell (AC) invasion, which is responsible for the development of the reproductive system (Garde et al, 2022).…”

Section: Mitochondrial Trafficking Dynamicsmentioning

confidence: 99%

“…During cell migration and invasion, the mitochondria have been found to localize to the leading edge of the cell to help drive cytoskeleton rearrangements (Madan et al, 2021). Anchor Cell (AC) invasion of the basement membrane (BM) in C. elegans requires mitochondrial recruitment to the invasive edge of the AC to drive invadopodia formation (Garde and Sherwood, 2021;Garde et al, 2022). Filamentous actin (F-actin) is responsible for the structure of the invadopodia and is increased by the presence of mitochondria at the invasive edge which provides a local source of ATP (Kelley et al, 2019).…”

Section: Leading Edge Mitochondria Can Rearrange the Cytoskeletonmentioning

confidence: 99%

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Mitochondrial trafficking and redox/phosphorylation signaling supporting cell migration phenotypes

Shannon

Gravelle

Cunniff

2022

Front. Mol. Biosci.

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Regulation of cell signaling cascades is critical in making sure the response is activated spatially and for a desired duration. Cell signaling cascades are spatially and temporally controlled through local protein phosphorylation events which are determined by the activation of specific kinases and/or inactivation of phosphatases to elicit a complete and thorough response. For example, A-kinase-anchoring proteins (AKAPs) contribute to the local regulated activity protein kinase A (PKA). The activity of kinases and phosphatases can also be regulated through redox-dependent cysteine modifications that mediate the activity of these proteins. A primary example of this is the activation of the epidermal growth factor receptor (EGFR) and the inactivation of the phosphatase and tensin homologue (PTEN) phosphatase by reactive oxygen species (ROS). Therefore, the local redox environment must play a critical role in the timing and magnitude of these events. Mitochondria are a primary source of ROS and energy (ATP) that contributes to redox-dependent signaling and ATP-dependent phosphorylation events, respectively. The strategic positioning of mitochondria within cells contributes to intracellular gradients of ROS and ATP, which have been shown to correlate with changes to protein redox and phosphorylation status driving downstream cellular processes. In this review, we will discuss the relationship between subcellular mitochondrial positioning and intracellular ROS and ATP gradients that support dynamic oxidation and phosphorylation signaling and resulting cellular effects, specifically associated with cell migration signaling.

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Section: Mitochondrial Trafficking Dynamicsmentioning

confidence: 99%

Section: Leading Edge Mitochondria Can Rearrange the Cytoskeletonmentioning

confidence: 99%

Mitochondrial trafficking and redox/phosphorylation signaling supporting cell migration phenotypes

Shannon

Gravelle

Cunniff

2022

Front. Mol. Biosci.

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“…PercevalHR (like many fluorescent biosensors) is sensitive to low pH, thus it is critical to ensure that changes in distribution or magnitude of ATP:ADP ratio detected in cells are not because of variations in intracellular pH. In ( Garde et al., 2022 ), we used the pH sensor Rosella ( Rosado et al., 2008 ) to independently verify that there were no pH gradients in the AC. However, the fluorescence spectra of Rosella (emission at ∼508 nm and 587 nm) overlap with that of PercevalHR, precluding simultaneous analyses of both the ATP:ADP ratio and pH in the AC.…”

Section: Limitationsmentioning

confidence: 99%

“…The protocol can be adapted to analyze the ATP:ADP ratios within other cell types in C. elegans . For complete details on the use and execution of this protocol, please refer to Garde et al. (2022) .…”

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confidence: 99%

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Visualizing cytoplasmic ATP in C. elegans larvae using PercevalHR

Garde

Sherwood²

2022

STAR Protocols

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Genetic characterization of C. elegansTMED genes

Navarro

Chamberlin

2023

Developmental Dynamics

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Backgroundp24/transmembrane Emp24 domain (TMED) proteins are a set of evolutionarily conserved, single pass transmembrane proteins that have been shown to facilitate protein secretion and selection of cargo proteins to transport vesicles in the cellular secretion pathway. However, their functions in animal development are incompletely understood.ResultsThe C. elegans genome encodes eight identified TMED genes, with at least one member from each defined subfamily (α, β, γ, δ). TMED gene mutants exhibit a shared set of defects in embryonic viability, animal movement, and vulval morphology. Two γ subfamily genes, tmed‐1 and tmed‐3, exhibit the ability to compensate for each other, as defects in movement and vulva morphology are only apparent in double mutants. TMED mutants also exhibit a delay in breakdown of basement membrane during vulva development.ConclusionsThe results establish a genetic and experimental framework for the study of TMED gene function in C. elegans, and argue that a functional protein from each subfamily is important for a shared set of developmental processes. A specific function for TMED genes is to facilitate breakdown of the basement membrane between the somatic gonad and vulval epithelial cells, suggesting a role for TMED proteins in tissue reorganization during animal development.

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Localized glucose import, glycolytic processing, and mitochondria generate a focused ATP burst to power basement-membrane invasion

Cited by 30 publications

References 91 publications

Mitochondrial trafficking and redox/phosphorylation signaling supporting cell migration phenotypes

Mitochondrial trafficking and redox/phosphorylation signaling supporting cell migration phenotypes

Visualizing cytoplasmic ATP in C. elegans larvae using PercevalHR

Genetic characterization of C. elegansTMED genes

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