Responses of photosynthetic organisms to sulfur starvation include (i) increasing the capacity of the cell for transporting and/or assimilating exogenous sulfate, (ii) restructuring cellular features to conserve sulfur resources, and (iii) modulating metabolic processes and rates of cell growth and division. We used microarray analyses to obtain a genome-level view of changes in mRNA abundances in the green alga Chlamydomonas reinhardtii during sulfur starvation. The work confirms and extends upon previous findings showing that sulfur deprivation elicits changes in levels of transcripts for proteins that help scavenge sulfate and economize on the use of sulfur resources. Changes in levels of transcripts encoding members of the light-harvesting polypeptide family, such as LhcSR2, suggest restructuring of the photosynthetic apparatus during sulfur deprivation. There are also significant changes in levels of transcripts encoding enzymes involved in metabolic processes (e.g., carbon metabolism), intracellular proteolysis, and the amelioration of oxidative damage; a marked and sustained increase in mRNAs for a putative vanadium chloroperoxidase and a peroxiredoxin may help prolong survival of C. reinhardtii during sulfur deprivation. Furthermore, many of the sulfur stress-regulated transcripts (encoding polypeptides associated with sulfate uptake and assimilation, oxidative stress, and photosynthetic function) are not properly regulated in the sac1 mutant of C. reinhardtii, a strain that dies much more rapidly than parental cells during sulfur deprivation. Interestingly, sulfur stress elicits dramatic changes in levels of transcripts encoding putative chloroplast-localized chaperones in the sac1 mutant but not in the parental strain. These results suggest various strategies used by photosynthetic organisms during acclimation to nutrient-limited growth.Sulfur (S) is an essential element present in proteins, lipids, and various metabolites. It is critical for the association of metal ions to proteins (electron carriers and redox controllers) and is a component of metabolites that function in photoprotection (14, 29) and signal transduction (such as in symbiosis) (45). Because most organisms have limited S storage, their growth and development is dependent upon a continuous supply of this nutrient from the environment. The majority of accessible S in soil solutions is in the form of the SO 4 2Ϫ anion. However, in some cases the majority of soil SO 4 2Ϫ may not be readily available to the biota, since the SO 4 2Ϫ anion is often complexed with cations as insoluble salts that are tightly adsorbed onto the surface of soil particles or exists as a soluble anion that rapidly leaches through the soil matrix. Furthermore, a large proportion of soil SO 4 2Ϫ may be covalently bonded to organic molecules in the form of sulfate esters and sulfonates.The acquisition of SO 4 2Ϫ by plants and microorganisms is facilitated by specific transport systems. Following uptake, the anion is either used for the direct sulfation of compounds or...