The VPS35 protein and the role of its impairments in mitochondrial dysfunction in Parkinson's disease.

The VPS35 is an essential protein that plays multifunctional roles in various biological processes. It is a core component of the retromer complex, involved in protein recycling from endosomes to the trans-Golgi network (TGN) and the plasma membrane. Besides its role as the retromer complex component, VPS35 interacts with many proteins and regulates mitochondrial homeostasis, mitochondrial dynamics (fusion and fission), and other important processes in various cell compartments. In the context of Parkinson's disease (PD) convincing evidence exists that VPS35 mutations, particularly [D620N], have a significant impact on normal retromer functioning, mitochondrial dysfunction, and impairment of neuronal health and survival. In this review we briefly consider structure and functions of the retromer complex, the role of VPS35 in mitochondria, and finally analyze physical and functional interactions of this protein with PD-important proteins associated with mitochondria.