ESYT1 tethers the ER to mitochondria and is required for mitochondrial lipid and calcium homeostasis.

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dc.creatorJaner, Alexandre
dc.creatorMorris, Jordan L
dc.creatorKrols, Michiel
dc.creatorAntonicka, Hana
dc.creatorAaltonen, Mari J
dc.creatorLin, Zhen-Yuan
dc.creatorAnand, Hanish
dc.creatorGingras, Anne-Claude
dc.creatorPrudent, Julien
dc.creatorShoubridge, Eric A
dc.date2024-01-19T00:31:09Z
dc.date2024-01
dc.date.accessioned2026-08-03T02:56:16Z
dc.descriptionMitochondria interact with the ER at structurally and functionally specialized membrane contact sites known as mitochondria-ER contact sites (MERCs). Combining proximity labelling (BioID), co-immunoprecipitation, confocal microscopy and subcellular fractionation, we found that the ER resident SMP-domain protein ESYT1 was enriched at MERCs, where it forms a complex with the outer mitochondrial membrane protein SYNJ2BP. BioID analyses using ER-targeted, outer mitochondrial membrane-targeted, and MERC-targeted baits, confirmed the presence of this complex at MERCs and the specificity of the interaction. Deletion of ESYT1 or SYNJ2BP reduced the number and length of MERCs. Loss of the ESYT1-SYNJ2BP complex impaired ER to mitochondria calcium flux and provoked a significant alteration of the mitochondrial lipidome, most prominently a reduction of cardiolipins and phosphatidylethanolamines. Both phenotypes were rescued by reexpression of WT ESYT1 and an artificial mitochondria-ER tether. Together, these results reveal a novel function for ESYT1 in mitochondrial and cellular homeostasis through its role in the regulation of MERCs.
dc.formatapplication/pdf
dc.identifier2575-1077
dc.identifierhttps://www.repository.cam.ac.uk/handle/1810/363483
dc.identifier2575-1077
dc.identifier.urihttps://repo.dare.co.zw/handle/123456789/170832
dc.languageeng
dc.publisherLife Science Alliance
dc.publisherMrc Mitochondrial Biology Unit
dc.publisherhttps://doi.org/10.26508/lsa.202302335
dc.rightsAttribution 4.0 International
dc.rightshttps://creativecommons.org/licenses/by/4.0/
dc.subjectCalcium
dc.subjectEndoplasmic Reticulum
dc.subjectHomeostasis
dc.subjectLipids
dc.subjectMitochondria
dc.subjectSynaptotagmins
dc.titleESYT1 tethers the ER to mitochondria and is required for mitochondrial lipid and calcium homeostasis.
dc.typeArticle

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