Beyond soluble electron carrier: cytochrome cM as a membrane-anchored redox regulator in cyanobacteria

Cytochrome c M is a small, highly conserved c -type cytochrome present across diverse cyanobacterial lineages, yet its true physiological function has puzzled researchers for over thirty years. Early efforts placed cytochrome c M as an alternative stress-induced electron carrier bridging photosynthetic and respiratory pathways. This view gained traction due to its widespread distribution, its dramatic induction during environmental stress, and the co-localisation of photosynthetic and respiratory complexes within the thylakoid membrane. However, careful biophysical characterisation revealed an exceptionally low midpoint redox potential (+151 mV) and remarkably slow electron-transfer kinetics towards P700 + —features that are inconsistent with efficient photosynthetic electron transfer. Likewise, direct evidence tying cytochrome c M to respiratory terminal oxidases has remained elusive and frequently contradictory. Interest in cytochrome c M has been reignited by recent physiological studies demonstrating that its removal markedly improves photosynthetic performance and carbon fixation under photomixotrophic conditions. Parallel bioinformatic and structural work has suggested the presence of an N-terminal transmembrane domain and revealed substantial structural similarity to the NorC subunit of bacterial nitric oxide reductases, setting cytochrome c M apart from classical soluble cytochromes. Here, we critically re-examine the historical models, weigh the evidence surrounding its candidate roles, and highlight the emerging concept that cytochrome c M functions primarily as a membrane-anchored redox regulator rather than a classical electron shuttle. Finally, we outline key knowledge gaps and suggest targeted strategies to resolve this long-standing enigma in cyanobacterial bioenergetics.