Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41467-021-21525-5
Keywords
-
Categories
Funding
- National Natural Science Foundation of China [81901166, 91854109, 31701170]
- Program for HUST Academic Frontier Youth Team [2018QYTD11]
Ask authors/readers for more resources
Upon starvation, cells switch to mitochondrial oxidation of fatty acids from glucose-based metabolism. VPS13D and ESCRT complex remodel lipid droplet (LD) membranes to promote fatty acid trafficking to mitochondria.
Upon starvation, cells rewire their metabolism, switching from glucose-based metabolism to mitochondrial oxidation of fatty acids, which require the transfer of FAs from lipid droplets (LDs) to mitochondria at mitochondria-LD membrane contact sites (MCSs). However, factors responsible for FA transfer at these MCSs remain uncharacterized. Here, we demonstrate that vacuolar protein sorting-associated protein 13D (VPS13D), loss-of-function mutations of which cause spastic ataxia, coordinates FA trafficking in conjunction with the endosomal sorting complex required for transport (ESCRT) protein tumor susceptibility 101 (TSG101). The VPS13 adaptor-binding domain of VPS13D and TSG101 directly remodels LD membranes in a cooperative manner. The lipid transfer domain of human VPS13D binds glycerophospholipids and FAs in vitro. Depletion of VPS13D, TSG101, or ESCRT-III proteins inhibits FA trafficking from LDs to mitochondria. Our findings suggest that VPS13D mediates the ESCRT-dependent remodeling of LD membranes to facilitate FA transfer at mitochondria-LD contacts. Metabolic rewiring requires the mobilization of fatty acids (FA) from lipid droplets (LDs) at membrane contact sites (MCSs), although the details of FA transfer remain unclear. Here, the authors show that VPS13D and the ESCRT complex remodel LD membranes to promote FA trafficking to mitochondria.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available