| First Author | Tajima K | Year | 2019 |
| Journal | Nat Metab | Volume | 1 |
| Issue | 9 | Pages | 886-898 |
| PubMed ID | 32313871 | Mgi Jnum | J:287367 |
| Mgi Id | MGI:6416065 | Doi | 10.1038/s42255-019-0106-z |
| Citation | Tajima K, et al. (2019) Mitochondrial lipoylation integrates age-associated decline in brown fat thermogenesis. Nat Metab 1(9):886-898 |
| abstractText | Thermogenesis in brown adipose tissue (BAT) declines with age; however, what regulates this process remains poorly understood. Here, we identify mitochondria lipoylation as a previously unappreciated molecular hallmark of aged BAT in mice. Using mitochondrial proteomics, we show that mitochondrial lipoylation is disproportionally reduced in aged BAT through a post-transcriptional decrease in the iron-sulfur (Fe-S) cluster formation pathway. A defect in the Fe-S cluster formation by the fat-specific deletion of Bola3 significantly reduces mitochondrial lipoylation and fuel oxidation in BAT, leading to glucose intolerance and obesity. In turn, enhanced mitochondrial lipoylation by alpha-lipoic acid supplementation effectively restores BAT function in old mice, thereby preventing age-associated obesity and glucose intolerance. The effect of alpha-lipoic acids requires mitochondrial lipoylation via the Bola3 pathway and does not depend on the anti-oxidant activity of alpha-lipoic acid. These results open up the possibility to alleviate the age-associated decline in energy expenditure by enhancing the mitochondrial lipoylation pathway. |
