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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
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received August 17, 2021.
- Accepted in final form August 17, 2022.
- © 2022 American Academy of Neurology
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