MFN2-driven mitochondria-to-nucleus tethering allows a non-canonical nuclear entry pathway of the mitochondrial pyruvate dehydrogenase complex.

Acetyl Coenzyme A / metabolism Cell Nucleus / genetics Lamins / metabolism Mitochondria / genetics Nuclear Envelope / metabolism Pyruvate Dehydrogenase Complex / genetics
acetylation cell cycle lamin metabolism mitochondria mitofusin nucleus protein trafficking pyruvate dehydrogenase complex tethering

Journal

Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571

Informations de publication

Date de publication:
03 03 2022
Historique:
received: 07 06 2021
revised: 15 11 2021
accepted: 01 02 2022
entrez: 4 3 2022
pubmed: 5 3 2022
medline: 14 4 2022
Statut: ppublish

Résumé

The mitochondrial pyruvate dehydrogenase complex (PDC) translocates into the nucleus, facilitating histone acetylation by producing acetyl-CoA. We describe a noncanonical pathway for nuclear PDC (nPDC) import that does not involve nuclear pore complexes (NPCs). Mitochondria cluster around the nucleus in response to proliferative stimuli and tether onto the nuclear envelope (NE) via mitofusin-2 (MFN2)-enriched contact points. A decrease in nuclear MFN2 levels decreases mitochondria tethering and nPDC levels. Mitochondrial PDC crosses the NE and interacts with lamin A, forming a ring below the NE before crossing through the lamin layer into the nucleoplasm, in areas away from NPCs. Effective blockage of NPC trafficking does not decrease nPDC levels. The PDC-lamin interaction is maintained during cell division, when lamin depolymerizes and disassembles before reforming daughter nuclear envelopes, providing another pathway for nPDC entry during mitosis. Our work provides a different angle to understanding mitochondria-to-nucleus communication and nuclear metabolism.

Identifiants

DOI: 10.1016/j.molcel.2022.02.003 PMID: 35245450
pubmed: 35245450
pii: S1097-2765(22)00108-3
doi: 10.1016/j.molcel.2022.02.003
pii:
doi:

Substances chimiques

Lamins 0
Pyruvate Dehydrogenase Complex 0
Acetyl Coenzyme A 72-89-9

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1066-1077.e7

Subventions

Organisme : CIHR
Pays : Canada

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2022 Elsevier Inc. All rights reserved.

Auteurs

Sotirios D Zervopoulos (SD)

Department of Medicine, University of Alberta, Edmonton, AB, Canada.

Aristeidis E Boukouris (AE)

Department of Medicine, University of Alberta, Edmonton, AB, Canada.

Bruno Saleme (B)

Department of Medicine, University of Alberta, Edmonton, AB, Canada.

Alois Haromy (A)

Department of Medicine, University of Alberta, Edmonton, AB, Canada.

Saymon Tejay (S)

Department of Medicine, University of Alberta, Edmonton, AB, Canada.

Gopinath Sutendra (G)

Department of Medicine, University of Alberta, Edmonton, AB, Canada. Electronic address: sutendra@ualberta.ca.

Evangelos D Michelakis (ED)

Department of Medicine, University of Alberta, Edmonton, AB, Canada. Electronic address: em2@ualberta.ca.

Articles similaires

Pathogenic mitochondrial DNA mutations inhibit melanoma metastasis.

Spencer D Shelton, Sara House, Luiza Martins Nascentes Melo et al.
1.00
DNA, Mitochondrial Humans Melanoma Mutation Neoplasm Metastasis

A dual role for PSIP1/LEDGF in T cell acute lymphoblastic leukemia.

Lisa Demoen, Filip Matthijssens, Lindy Reunes et al.
1.00
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Animals Mice Humans Cell Line, Tumor

Membrane potential stimulates ADP import and ATP export by the mitochondrial ADP/ATP carrier due to its positively charged binding site.

Vasiliki Mavridou, Martin S King, Andre Bazzone et al.
1.00
Adenosine Triphosphate Adenosine Diphosphate Mitochondrial ADP, ATP Translocases Binding Sites Mitochondria

High mitochondrial DNA levels accelerate lung adenocarcinoma progression.

Mara Mennuni, Stephen E Wilkie, Pauline Michon et al.
1.00
DNA, Mitochondrial Animals Adenocarcinoma of Lung Disease Progression Mice

Classifications MeSH

questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléotides › Ribonucléotides › Nucléotides adényliques › Coenzyme A › Acyl coenzyme A › Acétyl coenzyme A › MFN2-driven mitochondria-to-nucleus tethering...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Noyau de la cellule › MFN2-driven mitochondria-to-nucleus tethering...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines nucléaires › Protéines associées à la matrice nucléaire › Lamines › MFN2-driven mitochondria-to-nucleus tethering...
questionsmedicales.fr › Cellules › Structures cellulaires › Fractions subcellulaires › Mitochondries › MFN2-driven mitochondria-to-nucleus tethering...
questionsmedicales.fr › Cellules › Structures cellulaires › Fractions subcellulaires › Membranes intracellulaires › Enveloppe nucléaire › MFN2-driven mitochondria-to-nucleus tethering...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Complexes multienzymatiques › Complexe du pyruvate déshydrogénase › MFN2-driven mitochondria-to-nucleus tethering...