| First Author | Niemann J | Year | 2019 |
| Journal | Cell Calcium | Volume | 82 |
| Pages | 102055 | PubMed ID | 31377553 |
| Mgi Jnum | J:326309 | Mgi Id | MGI:7310142 |
| Doi | 10.1016/j.ceca.2019.102055 | Citation | Niemann J, et al. (2019) Cytosolic and mitochondrial Ca(2+) concentrations in primary hepatocytes change with ageing and in consequence of an mtDNA mutation. Cell Calcium 82:102055 |
| abstractText | Mitochondrial Ca(2+) flux is crucial for the regulation of cell metabolism. Ca(2+) entry to the mitochondrial matrix is mediated by VDAC1 and MCU with its regulatory molecules. We investigated hepatocytes isolated from conplastic C57BL/6NTac-mt(NODLtJ) mice (mtNOD) that differ from C57BL/6NTac mice (controls) by a point mutation in mitochondrial-encoded subunit 3 of cytochrome c oxidase, resulting in functional and morphological mitochondrial adaptations. Mice of both strains up to 12 months old were compared using mitochondrial GEM-GECO1 and cytosolic CAR-GECO1 expression to gain knowledge of age-dependent alterations of Ca(2+) concentrations. In controls we observed a significant increase in glucose-induced cytosolic Ca(2+) concentration with ageing, but only a minor elevation in mitochondrial Ca(2+) concentration. Conversely, glucose-induced mitochondrial Ca(2+) concentration significantly declined with ageing in mtNOD mice, paralleled by a slight decrease in cytosolic Ca(2+) concentration. This was consistent with a significant reduction of the MICU1 to MCU expression ratio and a decline in MCUR1. Our results can best be explained in terms of the adaptation of Ca(2+) concentrations to the mitochondrial network structure. In the fragmented mitochondrial network of ageing controls there is a need for high cytosolic Ca(2+) influx, because only some of the isolated mitochondria are in direct contact with the endoplasmic reticulum. This is not important in the hyper-fused elongated mitochondrial network found in ageing mtNOD mice which facilitates rapid Ca(2+) distribution over a large mitochondrial area. |
