NME3 binds to phosphatidic acid and mediates PLD6-induced mitochondrial tethering.
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:
02 10 2023
02 10 2023
Historique:
received:
20
01
2023
revised:
10
06
2023
accepted:
26
07
2023
medline:
17
8
2023
pubmed:
16
8
2023
entrez:
16
8
2023
Statut:
ppublish
Résumé
Mitochondria are dynamic organelles regulated by fission and fusion processes. The fusion of membranes requires elaborative coordination of proteins and lipids and is particularly crucial for the function and quality control of mitochondria. Phosphatidic acid (PA) on the mitochondrial outer membrane generated by PLD6 facilitates the fusion of mitochondria. However, how PA promotes mitochondrial fusion remains unclear. Here, we show that a mitochondrial outer membrane protein, NME3, is required for PLD6-induced mitochondrial tethering or clustering. NME3 is enriched at the contact interface of two closely positioned mitochondria depending on PLD6, and NME3 binds directly to PA-exposed lipid packing defects via its N-terminal amphipathic helix. The PA binding function and hexamerization confer NME3 mitochondrial tethering activity. Importantly, nutrient starvation enhances the enrichment efficiency of NME3 at the mitochondrial contact interface, and the tethering ability of NME3 contributes to fusion efficiency. Together, our findings demonstrate NME3 as a tethering protein promoting selective fusion between PLD6-remodeled mitochondria for quality control.
Identifiants
pubmed: 37584589
pii: 276187
doi: 10.1083/jcb.202301091
pmc: PMC10432850
pii:
doi:
Substances chimiques
Mitochondrial Proteins
0
NM23 Nucleoside Diphosphate Kinases
0
NME3 protein, human
EC 2.7.4.6
Phosphatidic Acids
0
Phospholipase D
EC 3.1.4.4
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2023 Su et al.
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