PERK recruits E-Syt1 at ER-mitochondria contacts for mitochondrial lipid transport and respiration.
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
06 03 2023
06 03 2023
Historique:
received:
02
06
2022
revised:
07
12
2022
accepted:
19
01
2023
entrez:
23
2
2023
pubmed:
24
2
2023
medline:
3
3
2023
Statut:
ppublish
Résumé
The integrity of ER-mitochondria appositions ensures transfer of ions and phospholipids (PLs) between these organelles and exerts crucial effects on mitochondrial bioenergetics. Malfunctions within the ER-mitochondria contacts altering lipid trafficking homeostasis manifest in diverse pathologies, but the molecular effectors governing this process remain ill-defined. Here, we report that PERK promotes lipid trafficking at the ER-mitochondria contact sites (EMCS) through a non-conventional, unfolded protein response-independent, mechanism. PERK operates as an adaptor for the recruitment of the ER-plasma membrane tether and lipid transfer protein (LTP) Extended-Synaptotagmin 1 (E-Syt1), within the EMCS. In resting cells, the heterotypic E-Syt1-PERK interaction endorses transfer of PLs between the ER and mitochondria. Weakening the E-Syt1-PERK interaction or removing the lipid transfer SMP-domain of E-Syt1, compromises mitochondrial respiration. Our findings unravel E-Syt1 as a PERK interacting LTP and molecular component of the lipid trafficking machinery of the EMCS, which critically maintains mitochondrial homeostasis and fitness.
Identifiants
pubmed: 36821088
pii: 213891
doi: 10.1083/jcb.202206008
pmc: PMC9998969
pii:
doi:
Substances chimiques
eIF-2 Kinase
EC 2.7.11.1
EIF2AK3 protein, human
EC 2.7.11.1
Phospholipids
0
Synaptotagmin I
0
SYT1 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2023 Sassano et al.
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