| First Author | Ouyang Q | Year | 2023 |
| Journal | Dev Cell | Volume | 58 |
| Issue | 4 | Pages | 289-305.e6 |
| PubMed ID | 36800997 | Mgi Jnum | J:359736 |
| Mgi Id | MGI:7443915 | Doi | 10.1016/j.devcel.2023.01.007 |
| Citation | Ouyang Q, et al. (2023) Rab8a as a mitochondrial receptor for lipid droplets in skeletal muscle. Dev Cell 58(4):289-305.e6 |
| abstractText | Dynamic interaction between lipid droplets (LDs) and mitochondria controls the mobilization of long-chain fatty acids (LCFAs) from LDs for mitochondrial beta-oxidation in skeletal muscle in response to energy stress. However, little is known about the composition and regulation of the tethering complex mediating LD-mitochondrion interaction. Here, we identify Rab8a as a mitochondrial receptor for LDs forming the tethering complex with the LD-associated PLIN5 in skeletal muscle. In rat L6 skeletal muscle cells, the energy sensor AMPK increases the GTP-bound active Rab8a that promotes LD-mitochondrion interaction through binding to PLIN5 upon starvation. The assembly of the Rab8a-PLIN5 tethering complex also recruits the adipose triglyceride lipase (ATGL), which couples LCFA mobilization from LDs with its transfer into mitochondria for beta-oxidation. Rab8a deficiency impairs fatty acid utilization and decreases endurance during exercise in a mouse model. These findings may help to elucidate the regulatory mechanisms underlying the beneficial effects of exercise on lipid homeostasis control. |
