| First Author | Daw CC | Year | 2020 |
| Journal | Cell | Volume | 183 |
| Issue | 2 | Pages | 474-489.e17 |
| PubMed ID | 33035451 | Mgi Jnum | J:298361 |
| Mgi Id | MGI:6477702 | Doi | 10.1016/j.cell.2020.08.049 |
| Citation | Daw CC, et al. (2020) Lactate Elicits ER-Mitochondrial Mg(2+) Dynamics to Integrate Cellular Metabolism. Cell 183(2):474-489.e17 |
| abstractText | Mg(2+) is the most abundant divalent cation in metazoans and an essential cofactor for ATP, nucleic acids, and countless metabolic enzymes. To understand how the spatio-temporal dynamics of intracellular Mg(2+) (iMg(2+)) are integrated into cellular signaling, we implemented a comprehensive screen to discover regulators of iMg(2+) dynamics. Lactate emerged as an activator of rapid release of Mg(2+) from endoplasmic reticulum (ER) stores, which facilitates mitochondrial Mg(2+) (mMg(2+)) uptake in multiple cell types. We demonstrate that this process is remarkably temperature sensitive and mediated through intracellular but not extracellular signals. The ER-mitochondrial Mg(2+) dynamics is selectively stimulated by L-lactate. Further, we show that lactate-mediated mMg(2+) entry is facilitated by Mrs2, and point mutations in the intermembrane space loop limits mMg(2+) uptake. Intriguingly, suppression of mMg(2+) surge alleviates inflammation-induced multi-organ failure. Together, these findings reveal that lactate mobilizes iMg(2+) and links the mMg(2+) transport machinery with major metabolic feedback circuits and mitochondrial bioenergetics. |
