This work rectifies the previous view that eukaryotic inositol lipids may derive from archaea that used such lipids together with membrane traffic proteins to engulf an aerobic bacterium, which became the mitochondrion. Eukaryotic biosynthesis of inositol lipids is of bacterial origin, as exemplified by the phylogeny of D-myo-inositol 3-phosphate synthase (MIPS), the initial enzyme of the biosynthetic pathway.

The merger of two very different microbes, an anaerobic archaeon and an aerobic bacterium, led to the birth of eukaryotic cells. Current models hypothesize that an archaeon engulfed bacteria through external protrusions that then fused together forming the membrane organelles of eukaryotic cells, including mitochondria. Images of cultivated Lokiarchaea sustain this concept, first proposed in the inside-out model which assumes that the membrane traffic system of archaea drove the merging with bacterial cells through membrane expansions containing inositol lipids, considered to have evolved first in archaea. This assumption has been evaluated here in detail. The data indicate that inositol lipids first emerged in bacteria, not in archaea. The implications of this finding for the models of eukaryogenesis are discussed.