ER-mitochondria distance is a critical parameter for efficient mitochondrial Ca²⁺ uptake and oxidative metabolism.

ABSTRACT: IP₃ receptor (IP₃R)-mediated Ca²⁺ transfer at the mitochondria-endoplasmic reticulum (ER) contact sites (MERCS) drives mitochondrial Ca²⁺ uptake and oxidative metabolism and is linked to different pathologies, including Parkinson's disease (PD). The dependence of Ca²⁺ transfer efficiency on the ER-mitochondria distance remains unexplored. Employing molecular rulers that stabilize ER-mitochondrial distances at 5 nm resolution, and using genetically encoded Ca²⁺ indicators targeting the ER lumen and the sub-mitochondrial compartments, we now show that a distance of ~20 nm is optimal for Ca²⁺ transfer and mitochondrial oxidative metabolism due to enrichment of IP₃R at MERCS. In human iPSC-derived astrocyte

SUBMITTER: Dematteis G 

PROVIDER: S-EPMC11467464 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature