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

Journal Article (Journal Article)

Invasive cells use transient, energy-consuming protrusions to breach basement membrane (BM) barriers. Using the ATP sensor PercevalHR during anchor cell (AC) invasion in Caenorhabditis elegans, we show that BM invasion is accompanied by an ATP burst from mitochondria at the invasive front. RNAi screening and visualization of a glucose biosensor identified two glucose transporters, FGT-1 and FGT-2, which bathe invasive front mitochondria with glucose and facilitate the ATP burst to form protrusions. FGT-1 localizes at high levels along the invasive membrane, while FGT-2 is adaptive, enriching most strongly during BM breaching and when FGT-1 is absent. Cytosolic glycolytic enzymes that process glucose for mitochondrial ATP production cluster with invasive front mitochondria and promote higher mitochondrial membrane potential and ATP levels. Finally, we show that UNC-6 (netrin), which polarizes invasive protrusions, also orients FGT-1. These studies reveal a robust and integrated energy acquisition, processing, and delivery network that powers BM breaching.

Full Text

Duke Authors

Cited Authors

  • Garde, A; Kenny, IW; Kelley, LC; Chi, Q; Mutlu, AS; Wang, MC; Sherwood, DR

Published Date

  • March 21, 2022

Published In

Volume / Issue

  • 57 / 6

Start / End Page

  • 732 - 749.e7

PubMed ID

  • 35316617

Pubmed Central ID

  • PMC8969095

Electronic International Standard Serial Number (EISSN)

  • 1878-1551

International Standard Serial Number (ISSN)

  • 1534-5807

Digital Object Identifier (DOI)

  • 10.1016/j.devcel.2022.02.019

Language

  • eng