Cristae junction as a fundamental switchboard for mitochondrial ion signaling and bioenergetics

OPA1 and MICU1 are both involved in the regulation of mitochondrial Ca²⁺ uptake and the stabilization of the cristae junction, which separates the inner mitochondrial membrane into the interboundary membrane and the cristae membrane. In this mini-review, we focus on the synergetic control of OPA1 and MICU1 on the cristae junction that serves as a fundamental regulator of multiple mitochondrial functions. In particular, we point to the critical role of an adaptive cristae junction permeability in mitochondrial Ca²⁺ signaling, spatial H⁺ gradients and mitochondrial membrane potential, metabolic activity, and apoptosis. These characteristics bear on a distinct localization of the oxidative phosphorylation machinery, the F_oF₁-ATPase, and mitochondrial Ca²⁺uniporter (MCU) within sections of the inner mitochondrial membrane isolated by the cristae junction and regulated by proteins like OPA1 and MICU1. We specifically focus on the impact of MICU1-regulated cristae junction on the activity and distribution of MCU within the complex ultrastructure of mitochondria.