SIRT5-mediated lysine desuccinylation regulates oxidative stress adaptation for intracellular infection of Magnaporthe oryzae

ABSTRACT: Plant-pathogenic fungi have developed kinds of detoxification strategies to suppress host reactive oxygen species (ROS) for colonization, but how this process is elaborately regulated has not been well revealed. Here we show that the SIRT5-mediated protein desuccinylation acts as a master regulator to regulate ROS detoxification in the rice blast fungus Magnaporthe oryzae. The sirtuin protein SIRT5 was identified as a desuccinylase in M. oryzae, deletion of which resulted in increased sensitivity to oxidative stress. Further analysis found that Sirt5 is important for fungal virulence and adaptation to host oxidative stress. Quantitative proteomics analysis under oxidative stress identified a large number of SIRT5-mediated succinylated proteins, most of which were mitochondrial proteins involved in oxidative phosphorylation, TCA cycle, fatty acid oxidation, etc. Many succinylated proteins were enzymes involved in different ROS de-toxification processes. Disruption of SIRT5 resulted in hypersuccinylation of detoxification-related enzymes, and significant reduction of NADPH/NADP+ and GSH/GSSG ratios, disrupting redox balance and impeding the expansion of invasive hyphae in the host. Interestingly, we proved that SIRT5 can desuccinylate thioredoxin Trx2 and glutathione peroxidase Hyr1 to activate its enzyme activity, probably by affecting its proper folding. Further analysis indicated that the succinylation sites of Trx2 (K144) and Hyr1 (K101, K127) were important for their function in ROS detoxification and virulence. Altogether, this work demonstrates a novel regulatory mechanism of SIRT5-mediated desuccinylation in detoxifying host ROS during M. oryzae infection.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Magnaporthe Oryzae (rice Blast Fungus) (pyricularia Oryzae)

TISSUE(S): Mycelial Cord

SUBMITTER: hong Hu  

LAB HEAD: Xiao-Lin Chen

PROVIDER: PXD044696 | Pride | 2024-03-06

REPOSITORIES: Pride