Death and the desaturase: Implication of Stearoyl-CoA desaturase-1 in the mechanisms of cell stress, apoptosis, and ferroptosis

• Published in: Biochimie 2024-10, Vol.225, p.156-167
• Main Author: Igal, R. Ariel
• Format: Article
• Language: English
• Subjects: apoptosis; autophagy; carbon; cell viability; death; endoplasmic reticulum; fatty acid composition; ferroptosis; lipids; mammals; stearoyl-CoA desaturase
• ISSN: 0300-9084; 1638-6183; 1638-6183
• DOI: 10.1016/j.biochi.2024.05.023

Growth and proliferation of normal and cancerous cells necessitate a finely-tuned regulation of lipid metabolic pathways to ensure the timely supply of structural, energetic, and signaling lipid molecules. The synthesis and remodeling of lipids containing fatty acids with an appropriate carbon length and insaturation level are required for supporting each phase of the mechanisms of cell replication and survival. Mammalian Stearoyl-CoA desaturases (SCD), particularly SCD1, play a crucial role in modulating the fatty acid composition of cellular lipids, converting saturated fatty acids (SFA) into monounsaturated fatty acids (MUFA) in the endoplasmic reticulum (ER). Extensive research has elucidated in great detail the participation of SCD1 in the molecular mechanisms that govern cell replication in normal and cancer cells. More recently, investigations have shed new light on the functional and regulatory role of the Δ9-desaturase in the processes of cell stress and cell death. This review will examine the latest findings on the involvement of SCD1 in the molecular pathways of cell survival, particularly on the mechanisms of ER stress and autophagy, as well in apoptotic and non-apoptotic cell death. •SCD1 activity is the main determinant of fatty acid composition in mammalian cells.•SCD1 activity controls the rate of both lipogenesis and lipid oxidation.•SCD1 facilitates a differential segregation of SFA and MUFA into cell lipids.•SCD1 is required for normal autophagy, but its precise role remains unknown.•SCD1 is a key and universal survival factor in both normal and cancer cells.