| First Author | Cho E | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 3586 |
| PubMed ID | 37328454 | Mgi Jnum | J:355740 |
| Mgi Id | MGI:7492856 | Doi | 10.1038/s41467-023-39343-2 |
| Citation | Cho E, et al. (2023) Ratiometric measurement of MAM Ca(2+) dynamics using a modified CalfluxVTN. Nat Commun 14(1):3586 |
| abstractText | Mitochondria-associated ER membrane (MAM) is a structure where these calcium-regulating organelles form close physical contact sites for efficient Ca(2+) crosstalk. Despite the central importance of MAM Ca(2+) dynamics in diverse biological processes, directly and specifically measuring Ca(2+) concentrations inside MAM is technically challenging. Here, we develop MAM-Calflux, a MAM-specific BRET-based Ca(2+) indicator. The successful application of the bimolecular fluorescence complementation (BiFC) concept highlights Ca(2+)-responsive BRET signals in MAM. The BiFC strategy imparts dual functionality as a Ca(2+) indicator and quantitative structural marker specific for MAM. As a ratiometric Ca(2+) indicator, MAM-Calflux estimates steady-state MAM Ca(2+) levels. Finally, it enables the visualization of uneven intracellular distribution of MAM Ca(2+) and the elucidation of abnormally accumulated MAM Ca(2+) from the neurons of Parkinson's disease mouse model in both steady-state and stimulated conditions. Therefore, we propose that MAM-Calflux can be a versatile tool for ratiometrically measuring dynamic inter-organellar Ca(2+) communication. |
