VIA1 is a conserved regulator of thylakoid membrane integrity that acts through VIPP1

Abstract

Thylakoid membranes are indispensable for oxygenic photosynthesis, yet the mechanisms that protect these membranes from photooxidative damage remain poorly understood. By screening previously uncharacterized proteins induced during the chloroplast unfolded protein response, we identify VIA1 as an essential factor for preserving thylakoid integrity under high light in the model green alga Chlamydomonas reinhardtii. Loss of VIA1 causes hypersensitivity to photo-oxidative stress and rapid thylakoid swelling. VIA1 localizes to thylakoid membranes and directly binds Vesicle-Inducing Protein in Plastids 1 (VIPP1), an ESCRT-III-like protein essential for thylakoid biogenesis and remodeling. Structure-guided mutagenesis shows that this interaction is required for VIA1 function and is mediated by a winged-helix domain interface reminiscent of ESCRT-II/ESCRT-III binding mode. VIA1 orthologs from cyanobacteria and land plants rescue the Chlamydomonas via1 mutant phenotype, and disruption of VIA1 in Synechocystis sp. PCC 6803 impairs growth, especially under light stress. Together, these findings establish VIA1 as an evolutionarily conserved protein that contributes to thylakoid membrane homeostasis via its interaction with VIPP1. Significance StatementFrom cyanobacteria to land plants, all organisms performing oxygenic photosynthesis rely on thylakoid membranes to capture light and and produce oxygen. Yet these membranes are highly susceptible to environmental stress, particularly excess light, which causes oxidative damage to membrane lipids and proteins. How thylakoid integrity is maintained under these conditions remains a key open question. Here we identify VIA1 as a conserved factor required for maintaining thylakoid membrane structure under high light. VIA1 interacts with VIPP1, an ESCRT-III-like protein essential for thylakoid biogenesis, through a functionally indispensable interface reminiscent of ESCRT-II/ESCRT-III binding mode. The conservation of the VIA1-VIPP1 module across photosynthetic prokaryotes and eukaryotes suggests it arose early in the evolution of oxygenic photosynthesis and has been maintained ever since.