Tao Guo, Lingyan Zhou, Min Xiong, Jing Xiong, Juan Huang, Yiming Li, Guoxin Zhang, Guiqin Chen, Zhi-Hao Wang, Tingting Xiao, Dan Hu, Anyu Bao, Zhentao Zhang
DJ-1, also known as Parkinson's disease protein 7 (Park7), is a multifunctional protein that regulates oxidative stress and mitochondrial function. Dysfunction of DJ-1 is implicated in the pathogenesis of Parkinson's disease (PD). Hyperhomocysteinemia is associated with an increased risk of PD. Here we show that homocysteine thiolactone (HTL), a reactive thioester of homocysteine (Hcy), covalently modifies DJ-1 on the lysine 182 (K182) residue in an age-dependent manner. The N-homocysteinylation (N-hcy) of DJ-1 abolishes its neuroprotective effect against oxidative stress and mitochondrial dysfunction, exacerbating cell toxicity...
February 21, 2024: Aging Cell