Interactions Between α-synuclein and Intact Mitochondria Studied by NMR

Abstract

The intrinsically disordered alpha-synuclein (α-synuclein) directly affects mitochondrial dynamics, morphology and function, and is closely related to Parkinson's disease. Studying the interactions between α-synuclein and mimic mitochondrial membranes/intact mitochondria is an effective way to understand how α-synuclein affects mitochondria. It has been reported that α-synuclein interacts with the mimic inner membrane of mitochondria (IMM), but not with the outer membrane of mitochondria (OMM), and the N-terminal plays an important role in binding with the mitochondria. However, little is known about the positions of interaction. Here, the interactions between α-synuclein and intact mitochondria isolated from rat liver were investigated by nuclear magnetic resonance (NMR). It was found that, different from the previous report, α-synuclein interacted with the OMM and the first 60 residues of N-terminus were crucial for the binding. It was postulated that the interaction between α-synuclein and OMM might depend not only on the lipid composition of the membrane, but also on other factors which were not reflected in the mimic membrane, such as the curvature of membrane and/or other components of the OMM. Our study also indicated that NMR is an effective method for studying the interaction of proteins with intact mitochondria.

Keywords

• nuclear magnetic resonance (nmr)
• α-synuclein
• intact mitochondria
• interaction