Regulatory Logic of the Chlamydomonas CO2-Concentrating Mechanism: Coupling Carbon Flux, Energy Supply, and Pyrenoid Architecture

Abstract The algal CO2-concentrating mechanism (CCM) elevates CO2 around Rubisco, the CO2-fixing enzyme, through the coordinated action of inorganic carbon (Ci) uptake systems, carbonic anhydrases (CAs), and CO2-retention mechanisms, thereby maintaining photosynthetic efficiency under CO2-limiting conditions. Although CCMs occur across diverse aquatic photosynthetic organisms, the green alga Chlamydomonas reinhardtii has become the principal model for dissecting the molecular regulation of the eukaryotic algal CCM, and this review focuses on regulatory mechanisms established in this organism. Recent studies have clarified energy-supply networks that support the CCM, including cyclic and pseudo-cyclic electron transfer, chloroplast–mitochondrial cooperation, and mitochondrial relocation toward the cell periphery during CCM induction, as well as multilayered regulatory circuits that tune CCM function across timescales. These circuits include CCM1/CIA5-dependent transcriptional control, Ca2+-binding protein CAS-dependent chloroplast Ca2+ signaling, protein relocalization, KEY1-dependent post-translational control of pyrenoid architecture, and active repression by the CCM1/CIA5-binding protein CBP1. However, these advances are still often discussed separately, and an explicit systems-level synthesis of carbon flux, energy supply, pyrenoid architecture, and regulation remains limited. Here, we describe the Chlamydomonas CCM as a coupled system in which Ci transport routes, CA deployment, CO2-retention mechanisms, electron-transfer pathways, and regulatory circuits are dynamically coordinated according to CO2 availability. We also discuss how far these regulatory layers may extend beyond Chlamydomonas within green algae, emphasizing the limited conservation of CCM1/CIA5- and LCR1-type transcriptional regulators and the presence of CAS-linked chloroplast Ca2+ signaling in both Chlamydomonas and land plants. Finally, we consider how this regulatory perspective can inform future CCM engineering, arguing that crop-oriented designs may ultimately need not only transferred pyrenoid components but also regulatory strategies that dynamically tune CCM activity according to carbon and energy status.