Vacuolar ATPase-mediated regulation of neutral lipid dynamics: Insights into lipid droplet homeostasis and stress response mechanisms

Biochim Biophys Acta Mol Cell Biol Lipids. 2024 Apr;1869(3):159465. doi: 10.1016/j.bbalip.2024.159465. Epub 2024 Feb 11.

Abstract

This study explores the intricate relationship between the yeast vacuolar H+-ATPase (V-ATPase) and neutral lipid metabolism. We show that LD generation observed upon loss of V-ATPase activity is crucial for survival in lipotoxic conditions. Moreover, the study uncovers a link between V-ATPase function, inositol metabolism and the activation of the oxidative pentose phosphate pathway, highlighting its pivotal role in counteracting oxidative stress. This work provides foundational insights into metabolic adaptations triggered by V-ATPase dysfunction, shedding light on cellular adaptability under lipotoxic and oxidative stress conditions.

Keywords: Inositol; Lipid droplet; Lipotoxicity; Oxidative stress response; Vacuolar ATPase.

MeSH terms

  • Homeostasis
  • Lipid Droplets / metabolism
  • Lipids
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Vacuolar Proton-Translocating ATPases* / metabolism

Substances

  • Saccharomyces cerevisiae Proteins
  • Vacuolar Proton-Translocating ATPases
  • Lipids