Membrane-bound organelles allow cells to traffic cargo and separate and regulate metabolic pathways. While many organelles are generated by the growth and division of existing organelles, some can also be produced de novo, often in response to metabolic cues. This review will discuss recent advances in our understanding of the early steps in the de novo biogenesis of peroxisomes, lipid droplets, lipoproteins, and autophagosomes. These organelles play critical roles in cellular lipid metabolism and other processes, and their dysfunction causes or is linked to several human diseases. The de novo biogenesis of these organelles occurs in or near the endoplasmic reticulum membrane. This review summarizes recent progress and highlights open questions.
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