An ESCRT-dependent step in fatty acid transfer from lipid droplets to mitochondria through VPS13D−TSG101 interactions
| العنوان: | An ESCRT-dependent step in fatty acid transfer from lipid droplets to mitochondria through VPS13D−TSG101 interactions |
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| المؤلفون: | Jingru Wang, Na Fang, Yuanjiao Du, Juan Xiong, Wei-Ke Ji, Yue Cao |
| المصدر: | Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021) Nature Communications |
| بيانات النشر: | Nature Portfolio, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Endosome, Science, Protein domain, Amino Acid Motifs, General Physics and Astronomy, macromolecular substances, Mitochondrion, Models, Biological, General Biochemistry, Genetics and Molecular Biology, ESCRT, Article, Fluorescence, Protein Structure, Secondary, 03 medical and health sciences, 0302 clinical medicine, Protein Domains, Lipid droplet, Chlorocebus aethiops, TSG101, Animals, Humans, Amino Acid Sequence, chemistry.chemical_classification, Multidisciplinary, Endosomal Sorting Complexes Required for Transport, Fatty Acids, Fatty acid, Proteins, General Chemistry, Energy metabolism, Lipid Droplets, Lipids, Cell biology, Mitochondria, ESCRT complex, DNA-Binding Proteins, 030104 developmental biology, HEK293 Cells, chemistry, COS Cells, Mutant Proteins, 030217 neurology & neurosurgery, Transcription Factors |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b02fcbe8ff065682c33766c01c2fe221Test https://doaj.org/article/03fa235d34f14508a5ddd8c3dd10f798Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b02fcbe8ff065682c33766c01c2fe221 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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