Overview of inorganic carbon uptake in the Chlamydomonas CCM. A, At ambient levels of CO₂ (300–500 ppm, 0.03–0.05%, 10–18 µM CO₂), extracellular inorganic carbon (Ci, i.e. CO₂ and hydrated Ci, such as $HCO3−$⁠) uptake is thought to be driven by drawdown of CO₂ into the chloroplast through rapid conversion of CO₂ to bicarbonate (⁠$HCO3−$⁠) by LCIB, which is dispersed throughout the stroma in a complex with LCIC. $HCO3−$ is then transported into the lumen of thylakoid tubules traversing the pyrenoid by bestrophin-like channels (BST1-3) on the pyrenoid periphery. Carbonic anhydrase 3 (CAH3) located in the lumen within the pyrenoid converts $HCO3−$ to CO₂, which diffuses into the surrounding Rubisco-EPYC1 matrix. CO₂ not assimilated by Rubisco is converted back to $HCO3−$ by LCIB. Periplasmic carbonic anhydrases 1 and 2 (CAH1/2) and the plasma membrane CO₂ channel low CO₂-inducible protein 1 (LCI1) assist with inward CO₂ diffusion (Fujiwara et al., 1990). Font sizes for CO₂ and $HCO3−$ represent their relative concentration. B, At sub-ambient CO₂ levels (<200 ppm, <0.03%, <7 µM CO₂), the CCM transitions to an active $HCO3−$ uptake system that relies on the $HCO3−$ channels HLA3 protein and LCIA at the plasma membrane and chloroplast envelope, respectively. The LCIB/C complex relocalizes the pyrenoid periphery, and may interact with BST1-3 to rapidly recapture leaked CO₂ as $HCO3−$ for re-uptake into the thylakoid lumen.