The absence of SIRT3 and SIRT5 promotes the acetylation of lens proteins and improves the chaperone activity of α-crystallin in mouse lenses.

Acetylation of lysine residues occurs in lens proteins. Previous studies have shown an improvement in the chaperone activity of αA-crystallin upon acetylation. Sirtuins are NAD+-dependent enzymes that can deacylate proteins. The roles of sirtuins in regulating the acetylation of lens proteins and their impacts on the function of α-crystallin are not known. Here, we detected sirtuin activity in mouse lenses, and SIRT3 and SIRT5 were present primarily in the mitochondria of cultured primary mouse lens epithelial cells. Western blotting showed higher levels of protein acetylation in the lenses of SIRT3 KO and SIRT5 KO mice than in lenses of WT mice. Mass spectrometry analyses revealed a greater number of acetylated lysine residues in α-crystallin isolated from the SIRT3 and SIRT5 KO lenses than from WT lenses. α-Crystallin isolated from SIRT3 and SIRT5 KO lenses displayed a higher surface hydrophobicity and higher chaperone activity than the protein isolated from WT lenses. Thus, SIRTs regulate the acetylation levels of crystallins in mouse lenses, and acetylation in lenses enhances the chaperone activity of α-crystallin.