Photorespiration benefits

Editorial https://doi.org/10.1038/s41477-026-02262-3 Photorespiration benefits Check for updates Photorespiration was long considered a futile cycle leading to a net carbon loss. However, evidence is accumulating that substantial metabolic benefits exist. T he key enzyme responsible for carbon fixation, ribulose-1, 5-bisphosphate carboxylase/oxygenase (RuBisCO), has an intrinsic oxygenase activity that results in the production of 2-phosphoglycolate (2PG) instead of 3-phosphoglycerate (3PGA). In the classical photorespiration pathway, two molecules of 2PG are recycled to 3PGA under loss of carbon dioxide, ammonia and chemical energy. This photorespiratory cycle involves multiple cell compartments, including the peroxisome, where glycolate is oxidized to glyoxylate and then transaminated to glycine, and the mitochondrion, where two molecules of glycine are metabolized to serine under release of carbon dioxide and ammonia. Serine is then converted in the peroxisome to hydroxypyruvate and further reduced to glycerate, which finally re-enters the chloroplast to be phosphorylated to 3PGA. As photorespiration leads to the net loss of carbon dioxide and chemical energy, there have been substantial efforts to engineer a RuBisCO with enhanced carboxylation efficiency, carbon-concentrating mechanisms that reduce oxygen concentration spatially around RuBisCO, or metabolic bypass reactions that reduce the energetic cost. Engineering plant RuBisCO is challenging as there is a trade-off between carboxylation efficiency and carbon dioxide affinity, and because it is a hetero-oligomer that requires species-specific chaperones and auxiliary factors for its assembly. Rather than optimizing the biochemical properties of RuBisCO itself, many species have evolved carbon-concentrating mechanisms that improve carboxylation efficiency by maintaining a high local carbon dioxide to oxygen ratio. Therefore, engineering carbon-concentrating mechanisms into crop species that did not evolve them is another strategy to mitigate photorespiration. Finally, bypass reactions can be engineered, such as relocation of the decarboxylation step from mitochondria to chloroplasts, which allows nature plants easier re-fixation of carbon dioxide, or the tartronyl-CoA pathway, which recycles 2PG to 3PGA in only three steps via tartronyl-CoA. Plastids in plants and green and red algae originated from a primary endosymbiosis of a eukaryotic host cell with a cyanobacterial precursor. Consequently, cyanobacteria have form I hetero-oligomeric RuBisCO that is composed of eight small subunits and eight large subunits, similar to that in plants. Like plant RuBisCO, the cyanobacterial form is prone to the oxygenation reaction, which is suppressed by the high local carbon dioxide to oxygen ratio within carboxysomes that have evolved as a carbon-concentrating mechanism. Nevertheless, even low levels of the oxygenation reaction require a photorespiratory pathway to metabolize 2PG in cyanobacteria1. In addition to the photorespiratory C2 cycle, cyanobacteria can directly metabolize glyoxylate to glycerate via the glycerate pathway, or sequentially decarboxylate glyoxylate fully via oxalate and formate1. Interestingly, engineering cyanobacteria to allow formate assimilation via serine did not result in improved efficiency of carbon fixation, but rather affected C1 metabolism and nitrogen assimilation and hence the carbon to nitrogen ratio2. Similar links between photorespiration on the one hand and C1 metabolism or nitrogen assimilation on the other hand are discussed for plants and suggest a benefit of photorespiration that obliterates the need for further evolutionary optimization of carboxylation efficiency or carbon-concentrating mechanisms for the abundant C3 species. For example, nitrogen assimilation is initiated by nitrate reductase in the cytosol, requiring NADH as a reducing equivalent. When photorespiration reduces the requirement for NADPH usage in the chloroplast Calvin–Benson–Bassham cycle, more reducing equivalents may be exported from the chloroplast through the malate valve, enabling enhanced nitrate reductase activity3. It has also been shown that photorespiration stimulates sulfur assimilation4. Sulfate is activated by ATP sulfurylase to adenosine 5′-phosphosulfate (APS), which is then reduced to sulfite and AMP by APS reductase. Sulfite is further reduced to sulfide by plastid sulfite reductase. Cysteine synthase joins sulfide and O-acetylserine to form cysteine, the first stable organic sulfur compound. Serine acetyltransferase, which acetylates serine to O-acetylserine, catalyses the rate-limiting step in cysteine synthesis, and photorespiration contributes to serine production. Furthermore, methionine is synthesized from cysteine via homocysteine and methionine synthase uses 5-methyltetrahydrofolate (5-methyl-THF) as a methyl donor and is therefore connected to photorespiration through C1 metabolism. Serine and glycine are metabolically interchangeable via serine hydroxymethyltransferase and 5,10-methylene-THF. During photorespiration, glycine decarboxylase and serine hydroxymethyltransferase cooperate in the mitochondria to convert two glycines to serine, carbon dioxide and ammonia. Therefore, photorespiration influences production of 5,10-methylene-THF and downstream C1 metabolism. The 5-methyl-THF is not only required for de novo methionine synthesis but also for regeneration of S-adenosylmethionine, the primary methyl donor in the cell. It was recently quantified using metabolic flux analysis that almost 6% of assimilated carbon passes through C1 metabolism under photorespiratory conditions, but not when photorespiration is suppressed5. This suggests that photorespiration could represent a substantial benefit to processes that depend on C1 metabolism, including methylation reactions. In this issue of Nature Plants, Valentin Hankofer from Helmholtz Munich and colleagues show that photorespiration indeed affects DNA methylation and that suppression of photorespiration changes the methylome6. These findings have not only consequences for engineering approaches that aim to reduce photorespiration in C3 plants, but also for projecting the consequences of increased atmospheric carbon dioxide concentrations in the future. It was discussed that reduced leaf nitrogen content due to increased carbon dioxide concentrations may be caused by enhanced photosynthetic nitrogen use efficiency and therefore a lower nitrogen requirement, rather than being a dilution effect of enhanced growth7. Given that suppression of photorespiration leads to reduced nitrogen and sulfur assimilation as well as reduced C1 metabolism, which are all required for amino Volume 12 | March 2026 | 481–482 | 481 Editorial acid biosynthesis, it remains to be seen whether reduced nitrogen requirement will outweigh protein synthesis potential, or vice versa, in future climate scenarios. Published online: 24 March 2026 nature plants (...truncated)