Evolution of the endomembrane system, mitochondrion, and eukaryote cell size. A - F. Model for evolution of the endomembrane system in response to imbalances in plasma membrane activities. Archaeal cells, containing co-translationally active ribosomes, are exposed to an environmental stressor (here exemplified by external H2O2, orange background, although UV radiation and/or desiccation may provide additional sources of stress). The plasma membrane was particularly affected by this external injury. As a result of the peripheral damage, a vesicle carrying molecular components (e.g., ribosomes) pinched off from the plasma membrane and accumulated in the inner cell, giving rise to the proto-ER. H2O2 that infiltrated the cell was cleared by enzymes (e.g., catalases and peroxidases). This generated a protected intracellular zone (white) that allowed proliferation of the proto-ER and associated ribosomes, while H2O2-damaged co-translational targeting gradually disappeared from the plasma membrane. Vesicular traffic, scaffolded by the incipient cytoskeleton (microtubule-organizing center and microtubules in red), emerged as an exocytic avenue to target ER-synthesized proteins to the plasma membrane (E and F). G - K. Putative model for early events in mitochondrial evolution. In a biofilm, archaeal and alphaprotobacterial cells are juxtaposed in a syntrophic association (arrows). Fusogenic and membrane remodeling activities necessary for cell-cell fusions during archaeal mating allowed the capture and retention of the alphaproteobacterium precursor of mitochondria. Environmental O2 (blue background) penetrates the cells and is photo-activated to ROS by UV. Alphaproteobacterial aerobic respiration clears the intracellular O2 (white zones). Intracellular mitochondria propagate and deliver ATP to the cytoplasm (J and H). Increase in cell size (E, F and J, K) emerges as a crucial eukaryotic strategy to counterbalance the influx of oxygenic species.