Conserved and divergent mechanisms by which endoplasmic reticulum stress reprograms lipid metabolism in microalgae

The endoplasmic reticulum (ER) is a central hub coordinating protein homeostasis and lipid metabolism in eukaryotic cells. In microalgae, which inhabit highly fluctuating environments, ER stress is increasingly recognized as a driver of lipid remodeling rather than a secondary metabolic consequence. This review synthesizes recent advances in ER stress signaling in microalgae, focusing on Chlamydomonas reinhardtii, and places these findings in a comparative eukaryotic context. Microalgae retain a conserved, IRE1-centered unfolded protein response (UPR) while lacking auxiliary branches found in animals and land plants. Activation of ER stress induces extensive reprogramming of membrane lipid composition, fatty acid desaturation, sterol metabolism, and triacylglycerol (TAG) accumulation. Notably, the Chlamydomonas IRE1/bZIP1 pathway functions to restrain excessive TAG accumulation, thereby prioritizing membrane adaptation and ER homeostasis. The graded and dynamic nature of this response likely compensates for the simplified single-sensor architecture by enabling flexible modulation of downstream outputs depending on stress intensity and duration. Importantly, ER stress responses exhibit distinct modes depending on stress severity: moderate stress promotes adaptive membrane stabilization, whereas severe or prolonged stress redirects membrane-derived fatty acids into TAG for sequestration. This lipid-centered adaptation contrasts with land plants, which stabilize membrane composition without substantial TAG accumulation, and with yeast and animals, where membrane biogenesis and neutral lipid storage occur in parallel, with distinct regulatory features. By integrating insights across eukaryotes, this review highlights ER stress as a framework for understanding lipid remodeling in microalgae and discusses how UPR manipulation may enable rational engineering of lipid production platforms.