Super-resolution microscopies, technological breakthrough to decipher mitochondrial structure and dynamic.

Mitochondria are complex organelles with an outer membrane enveloping a second inner membrane that creates a vast matrix space partitioned by pockets or cristae that join the peripheral inner membrane with several thin junctions. Several micrometres long, mitochondria are generally close to 300 nm in diameter, with membrane layers separated by a few tens of nanometres. Ultrastructural data from electron microscopy revealed the structure of these mitochondria, while conventional optical microscopy revealed their extraordinary dynamics through fusion, fission, and migration processes but its limited resolution power restricted the possibility to go further. By overcoming the limits of light diffraction, Super-Resolution Microscopy (SRM) now offers the potential to establish the links between the ultrastructure and remodelling of mitochondrial membranes, leading to major advances in our understanding of mitochondria's structure-function. Here we review the contributions of SRM imaging to our understanding of the relationship between mitochondrial structure and function. What are the hopes for these new imaging approaches which are particularly important for mitochondrial pathologies?

Non-canonical interplay between glutamatergic NMDA and dopamine receptors shapes synaptogenesis.

Direct interactions between receptors at the neuronal surface have long been proposed to tune signaling cascades and neuronal communication in health and disease. Yet, the lack of direct investigation methods to measure, in live neurons, the interaction between different membrane receptors at the single molecule level has raised unanswered questions on the biophysical properties and biological roles of such receptor interactome. Using a multidimensional spectral single molecule-localization microscopy (MS-SMLM) approach, we monitored the interaction between two membrane receptors, i.e. glutamatergic NMDA (NMDAR) and G protein-coupled dopamine D1 (D1R) receptors. The transient interaction was randomly observed along the dendritic tree of hippocampal neurons. It was higher early in development, promoting the formation of NMDAR-D1R complexes in an mGluR5- and CK1-dependent manner, favoring NMDAR clusters and synaptogenesis in a dopamine receptor signaling-independent manner. Preventing the interaction in the neonate, and not adult, brain alters in vivo spontaneous neuronal network activity pattern in male mice. Thus, a weak and transient interaction between NMDAR and D1R plays a structural and functional role in the developing brain.