Hog1 plays a role in regulating lipid droplet homeostasis.

Hog1, the high-osmolarity glycerol response protein, is a crucial protein that responds to hypertonicity by enhancing glycerol production, subsequently raising intracellular osmotic pressure to resist hyperosmotic stress and protect cells. In this work, I uncover a previously unknown function of Hog1: regulating the deposition of lipid droplets. In my previous research, I discovered that in a glucose-rich medium, The Candida albicans vip1Δ/Δ strain, which lacks the inositol hexakisphosphate kinase gene, exhibits marked accumulation of lipid droplets, ultimately culminating in cell death. In this study, I found that overexpressing HOG1 could alleviate the excessive accumulation of lipid droplets and prevent cell death. Further investigation revealed that neither the knockout nor overexpression of HOG1 affected the energy homeostasis of the vip1Δ/Δ, but instead, modulated the osmotic pressure balance within the cell to regulate lipid droplet aggregation. Interestingly, in wild-type (WT) strains, neither HOG1 overexpression nor exposure to hypertonic stimuli altered intracellular lipid droplet levels. However, upon treatment with oleic acid (OA), which promotes lipid droplet accumulation in WT cells, HOG1 overexpression significantly reduced the extent of this accumulation. This observation underscores Hog1's ability to modulate lipid droplet metabolism specifically in C. albicans strains that are prone to excessive lipid droplet accumulation. In summary, my study unveils a previously unrecognized function of Hog1 in regulating lipid droplet homeostasis in C. albicans, particularly in contexts where lipid droplet accumulation is prominent, emphasizing its multifaceted role in cellular adaptation and stress response.