Mitochondria–endoplasmic reticulum (ER) communication is organized through specialized contact sites (MERCS), which act as dynamic signaling platforms integrating many of the processes that fail early in neurodegeneration, including calcium handling, lipid homeostasis, organelle quality control, and stress adaptation. Rather than being passive structures, MERCS actively shape how cells respond to stress and can bias the balance between survival and regulated cell death. Emerging evidence indicates that MERCS remodeling occurs before pathological hallmarks, making these contact sites early indicators of cellular dysfunction, acting as cellular “health meters”.  Defining how MERCS composition and dynamics shift during the transition from healthy to vulnerable states may therefore reveal early mechanisms of neuronal and glial susceptibility. These features make MERCS a promising point of intervention, where adjusting their organization can modulate how cells cope with stress and their vulnerability to cell death. In this context, identifying MERCS modulators, from endogenous proteins and lipids to small molecules, offers new ways to reduce organelle stress, limit cell death, and preserve neuronal and glial function.

More information:

• https://www.achucarro.org/laboratory/neuropathology-of-interorganellar-contact-sites/