Cilia and flagella are antenna‑like organelles that project from the cell surface and are widely distributed from unicellular eukaryotes to mammals. Motile cilia must beat in a coordinated manner to generate productive fluid flow and drive cell motility, which is essential for processes such as sperm propulsion, mucociliary clearance in the airways, and cerebrospinal fluid circulation. When this coordination breaks down, it leads to primary ciliary dyskinesia (PCD), situs inversus, hydrocephalus, and other ciliopathies, yet the signaling mechanisms that orchestrate ciliary coordination have long remained elusive.

Recently, a research group led by Prof. HUANG Kaiyao from the Institute of Hydrobiology (IHB) of the Chinese Academy of Sciences uncovered a novel mechanism by which redox signals couple with calcium dynamics and coordinate flagellar beating. This study was published in PNAS.

Using the biflagellate green alga Chlamydomonas reinhardtii as a model, the researchers identified CYB5D1 as an evolutionarily conserved heme‑binding axonemal protein that functions as a redox‑sensitive switch. The Asp58 residue in CYB5D1 is critical for heme binding; loss of CYB5D1 or the Asp58Gly point mutation shifts the intraflagellar redox potential toward a more reduced state and elevates Ca²⁺ spike frequency specifically in the cis‑flagellum.

Through high‑resolution live‑cell imaging, the researchers found that oxidative treatment induces coupled Ca²⁺ spikes between the two flagella and restores coordinated beating, whereas reductive treatment uncouples these spikes and impairs coordination. This demonstrates that redox signals act upstream of Ca²⁺ to control flagellar dominance and waveform modification.

“We have established CYB5D1 as a critical integrator that converts redox dynamics into Ca²⁺‑mediated mechanical dominance switching,” said Prof. Huang. “This is the first molecular mechanism directly linking redox and Ca²⁺ signaling in the regulation of ciliary motility.”

This study not only provides a new conceptual framework for understanding how cilia achieve coordinated beating, but also opens avenues for mechanistic dissection and therapeutic intervention in ciliopathies, including primary ciliary dyskinesia.

CYB5D1 integrates redox signals to control Flagellar coordination through calcium dynamics (Image by IHB)

(Editor: MA Yun)