Mitochondrial dysfunction and
ubiquitin-
proteasome system (UPS) failure contribute significantly to the development of
Parkinson's disease (PD). The
proteasome subunit Rpn13 located on the regulatory (19S) subparticle play an important role in the delivery of
proteins, subjected to degradation, to the proteolytic (20S) part of
proteasome. We have previously found several brain
mitochondrial proteins specifically bound to Rpn13 (Buneeva et al. (2020) Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry, 14, 297-305). In this study we have investigated the effect of the
neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (
MPTP) and the neuroprotector
isatin on the mitochondrial subproteome of Rpn13-binding
proteins of the mouse brain. Administration of
MPTP (30 mg/kg) to animals caused
movement disorders typical of PD, while pretreatment with
isatin (100 mg/kg, 30 min before
MPTP) reduced their severity. At the same time, the injection of
MPTP,
isatin, or their combination (
isatin +
MPTP) had a significant impact on the total number and the composition of Rpn13-binding
proteins. The injection of
MPTP decreased the total number of Rpn13-binding
proteins in comparison with control, and the injection of
isatin prior to
MPTP or without
MPTP caused an essential increase in the number of Rpn13-binding
proteins, mainly of the functional group of
proteins participating in the
protein metabolism regulation, gene expression, and differentiation. Selected biosensor validation confirmed the interaction of Rpn13 subunit of
proteasome with some
proteins (
glyceraldehyde-3-phosphate dehydrogenase,
pyruvate kinase,
histones H2A and H2B) revealed while proteomic profiling. The results obtained testify that under the conditions of experimental
MPTP-induced parkinsonism the
neuroprotective effect of
isatin may be aimed at the interaction of mitochondria with the components of UPS.