What Is the Role of Organelle Membrane Contact Sites in Neurodegenerative Diseases?

Cells depend on membrane-bound organelles for their normal function and survival. Compartmentalization within the endoplasmic reticulum (ER), Golgi apparatus, secretory vesicles, endosomes, lysosomes, mitochondria, lipid droplets, and peroxisomes allows each organelle to maintain a distinct environment required for their specific functions. However, these organelles interact with each other through membrane contact sites, which enable their cross-talk and cooperation required for cellular homeostasis (Figure). These membrane contact sites are critical for transfer of lipids and ions such as calcium (Ca2+), for cell metabolism, and for regulation of organelle dynamics.(1-6) Tethering at membrane contact sites involves macromolecular complexes consisting of proteins or lipids.(7-11) Whereas dysfunction of individual organelles has been linked with several neurodegenerative disorders, impaired regulation of organelle cross-talk is emerging as an important disease mechanism in such disorders, including hereditary spastic paraplegia (HSP), Parkinson disease (PD), and others.(12-17) Targeting organelle contact sites may thus provide a potential therapeutic approach in these disorders. This topic has been recently reviewed.(18)

Automated summary

Cells rely on membrane-bound organelles for their normal function and survival. These organelles interact with each other through membrane contact sites, enabling their cross-talk and cooperation for cellular homeostasis. The membrane contact sites are critical for lipid and calcium transfer, cell metabolism, and regulation of organelle dynamics. Dysfunction of organelle cross-talk is emerging as an important mechanism in neurodegenerative disorders, suggesting that targeting organelle contact sites could be a potential therapeutic approach.