Modulating organelle membrane contact sites using small molecules
Organelle membrane contact sites are emerging as druggable signaling hubs, whose pathological hypo- or hypercoupling drives neurodegenerative, metabolic, and oncogenic disease states.
A unifying therapeutic framework classifies small molecules as membrane contact site stabilizers, which restore impaired contacts, or destabilizers, which relieve pathological hypercoupling across disease contexts.
Small molecules regulate organelle membrane contact sites by inducing distinct conformational states of tether proteins, thereby reshaping local interaction networks.
Recent advances in chemoproteomics, live-cell imaging, and structural biology have made it possible to systematically discover membrane contact site regulators and analyze their mechanisms in complex cellular environments.
https://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(26)00041-6
