Deacetylation of ACO2 Is Essential for Inhibiting Bombyx mori Nucleopolyhedrovirus Propagation

Abstract

Bombyx mori nucleopolyhedrovirus (BmNPV) is a specific pathogen of Bombyx mori that can significantly impede agricultural development. Accumulating evidence indicates that the viral proliferation in the host requires an ample supply of energy. However, the correlative reports of baculovirus are deficient, especially on the acetylation modification of tricarboxylic acid cycle (TCA cycle) metabolic enzymes. Our recent quantitative analysis of protein acetylome revealed that mitochondrial aconitase (ACO2) could be modified by (de)acetylation at lysine 56 (K56) during the BmNPV infection; however, the underlying mechanism is yet unknown. In order to understand this regulatory mechanism, the modification site K56 was mutated to arginine (Lys56Arg; K56R) to mimic deacetylated lysine. The results showed that mimic deacetylated mitochondrial ACO2 restricted enzymatic activity. Although the ATP production was enhanced after viral infection, K56 deacetylation of ACO2 suppressed BmN cellular ATP levels and mitochondrial membrane potential by affecting citrate synthase and isocitrate dehydrogenase activities compared with wild-type ACO2. Furthermore, the deacetylation of exogenous ACO2 lowered BmNPV replication and generation of progeny viruses. In summary, our study on ACO2 revealed the potential mechanism underlying WT ACO2 promotes the proliferation of BmNPV and K56 deacetylation of ACO2 eliminates this promotional effect, which might provide novel insights for developing antiviral strategies.

Beyond Histones: Unveiling the Functional Roles of Protein Acetylation in Prokaryotes and Eukaryotes

“…Furthermore, studies have identified numerous acetylation sites within TCA cycle proteins. These modifications can influence protein activity, with some experiencing increased activity and others experiencing decreased activity [19,40,41]. For example, acetylation of A.…”

“…Furthermore, studies have identified numerous acetylation sites within TCA cycle proteins. These modifications can influence protein activity, with some experiencing increased activity and others experiencing decreased activity [19, 40, 41]. For example, acetylation of A. thaliana malate dehydrogenase at K169, K170, and K334 decreases its oxoacetate reduction activity [42], while acetylation of E. coli and H. sapiens at K99/K140 and K307, respectively, increases its enzymatic activity [43].…”