The importance of being connected: membrane contact sites and Parkinson's disease.

Membrane contact sites (MCS) occur between closely apposed organelles and are a means to transport ions and macromolecules between themselves, co-ordinate cellular metabolism, and direct organelle fission and transport. While MCS between the endoplasmic reticulum (ER) and mitochondria has long been investigated, the importance of MCS in both lipid droplet (LD) function and the endolysosomal system are now being recognized. The identification of VPS13C and LRRK2 at MCS, protein products of the familial Parkinson's disease (PD) loci PARK23 and PARK8, respectively, and the well-established dysfunction of the endolysosomal system and mitochondria in disease pathogenesis, arguably put PD at the forefront of MCS involvement in neurological disease.