Serine palmitoyltransferase assembles at ER-mitochondria contact sites.
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
25
10
2021
revised:
01
11
2021
accepted:
03
11
2021
entrez:
17
11
2021
pubmed:
18
11
2021
medline:
29
3
2022
Statut:
epublish
Résumé
The accumulation of sphingolipid species in the cell contributes to the development of obesity and neurological disease. However, the subcellular localization of sphingolipid-synthesizing enzymes is unclear, limiting the understanding of where and how these lipids accumulate inside the cell and why they are toxic. Here, we show that SPTLC2, a subunit of the serine palmitoyltransferase (SPT) complex, catalyzing the first step in de novo sphingolipid synthesis, localizes dually to the ER and the outer mitochondrial membrane. We demonstrate that mitochondrial SPTLC2 interacts and forms a complex in trans with the ER-localized SPT subunit SPTLC1. Loss of SPTLC2 prevents the synthesis of mitochondrial sphingolipids and protects from palmitate-induced mitochondrial toxicity, a process dependent on mitochondrial ceramides. Our results reveal the in trans assembly of an enzymatic complex at an organellar membrane contact site, providing novel insight into the localization of sphingolipid synthesis and the composition and function of ER-mitochondria contact sites.
Identifiants
pubmed: 34785538
pii: 5/2/e202101278
doi: 10.26508/lsa.202101278
pmc: PMC8605320
pii:
doi:
Substances chimiques
Multienzyme Complexes
0
Serine C-Palmitoyltransferase
EC 2.3.1.50
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2021 Aaltonen et al.
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