---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '21378'
abstract:
- lang: eng
  text: From insects to mammals, essential brain functions, such as forming long-term
    memories (LTMs), increase metabolic activity in stimulated neurons to meet the
    energetic demand associated with brain activation. However, while impairing neuronal
    metabolism limits brain performance, whether expanding the metabolic capacity
    of neurons boosts brain function remains poorly understood. Here, we show that
    LTM formation of flies and mice can be enhanced by increasing mitochondrial metabolism
    in central memory circuits. By knocking down the mitochondrial Ca2+ exporter Letm1,
    we favour Ca2+ retention in the mitochondrial matrix of neurons due to reduction
    of mitochondrial H+/Ca2+ exchange. The resulting increase in mitochondrial Ca2+
    over-activates mitochondrial metabolism in neurons of central memory circuits,
    leading to improved LTM storage in training paradigms in which wild-type counterparts
    of both species fail to remember. Our findings unveil an evolutionarily conserved
    mechanism that controls mitochondrial metabolism in neurons and indicate its involvement
    in shaping higher brain functions, such as LTM.
acknowledgement: We thank all members of the laboratory of J.d.J.-S. for insightful
  discussions and comments. We thank S. Perez for technical assistance. This work
  was made possible by the Paris Brain Institute Diane Barriere Chair in Synaptic
  Bioenergetics awarded to J.d.J.-S., who is also supported by an ERC Starting Grant
  (SynaptoEnergy, European Research Council; ERC-StG-852873), 2019 ATIP-Avenir Grant
  (CNRS, Inserm), a Big Brain Theory Grant (ICM Foundation) and a Kavli Exploratory
  Award (Kavli Foundation). This work was also supported by an ERC Advanced Grant
  (EnergyMeMo; ERC-AdG-741550) to T.P. and grants from the Agence Nationale de la
  Recherche to P.Y.P. (ANR-20-CE92-0047-01), T.P. (ANR-23-CE16-0029-01), A.P. and
  J.d.J.-S. (ANR-22-CE16-0020) and J.d.J.-S. (ANR-24-CE16-0221). T.P., P.Y.P. and
  J.d.J.-S. are permanent CNRS researchers. A.P. is a permanent ESPCI associate professor.
  T.C. was funded by the French Ministry of Research and the Fondation pour la Recherche
  Médicale. V.R. was funded by the Max Planck Society, the Chan Zuckerberg Initiative
  DAF, an advised fund of the Silicon Valley Community Foundation grant number 2024-349543
  and the NIH Director’s New Innovator Award (DP2 MH140148). A.B.-G. and C.R.-D. received
  funding from an ERC Starting Grant (HighMemory; ERC-StG-948217), the Ministry of
  Economy and Competitiveness (PID2021-122795OB-I00) and the Departament d’Economia
  i Coneixement de la Generalitat de Catalunya (SGR 00022). T.P.V. was funded by the
  Wellcome Trust and a Royal Society Sir Henry Dale Research Fellowship (WT100000)
  and a Wellcome Trust Senior Research Fellowship (214316/Z/18/Z). K.G. was supported
  by the DIM C-BRAINS, funded by the Conseil Régional d’Ile-de-France. The contributions
  of H.F. and E.R.S. were supported by the Howard Hughes Medical Institute. The PHENO-ICMice
  animal Core at ICM is supported by two ‘Investissements d’avenir’ (ANR-10- IAIHU-06
  and ANR-11-INBS-0011-NeurATRIS) and the Fondation pour la Recherche Médicale.
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Anjali
  full_name: Amrapali Vishwanath, Anjali
  last_name: Amrapali Vishwanath
- first_name: Typhaine
  full_name: Comyn, Typhaine
  last_name: Comyn
- first_name: Rodrigo G.
  full_name: Mira, Rodrigo G.
  last_name: Mira
- first_name: Claire
  full_name: Brossier, Claire
  last_name: Brossier
- first_name: Carlos
  full_name: Pascual-Caro, Carlos
  last_name: Pascual-Caro
- first_name: Maya
  full_name: Faour, Maya
  last_name: Faour
- first_name: Kahina
  full_name: Boumendil, Kahina
  last_name: Boumendil
- first_name: Chaitanya
  full_name: Chintaluri, Chaitanya
  id: BA06AFEE-A4BA-11EA-AE5C-14673DDC885E
  last_name: Chintaluri
  orcid: 0000-0003-4252-1608
- first_name: Carla
  full_name: Ramon-Duaso, Carla
  last_name: Ramon-Duaso
- first_name: Ruolin
  full_name: Fan, Ruolin
  last_name: Fan
- first_name: Kishalay
  full_name: Ghosh, Kishalay
  last_name: Ghosh
- first_name: Helen
  full_name: Farrants, Helen
  last_name: Farrants
- first_name: Jean-Paul
  full_name: Berwick, Jean-Paul
  last_name: Berwick
- first_name: Riya
  full_name: Sivakumar, Riya
  last_name: Sivakumar
- first_name: Mario
  full_name: Lopez-Manzaneda, Mario
  last_name: Lopez-Manzaneda
- first_name: Eric R.
  full_name: Schreiter, Eric R.
  last_name: Schreiter
- first_name: Thomas
  full_name: Preat, Thomas
  last_name: Preat
- first_name: Tim P
  full_name: Vogels, Tim P
  id: CB6FF8D2-008F-11EA-8E08-2637E6697425
  last_name: Vogels
  orcid: 0000-0003-3295-6181
- first_name: Vidhya
  full_name: Rangaraju, Vidhya
  last_name: Rangaraju
- first_name: Arnau
  full_name: Busquets-Garcia, Arnau
  last_name: Busquets-Garcia
- first_name: Pierre-Yves
  full_name: Plaçais, Pierre-Yves
  last_name: Plaçais
- first_name: Alice
  full_name: Pavlowsky, Alice
  last_name: Pavlowsky
- first_name: Jaime
  full_name: de Juan-Sanz, Jaime
  last_name: de Juan-Sanz
citation:
  ama: Amrapali Vishwanath A, Comyn T, Mira RG, et al. Mitochondrial Ca2+ efflux controls
    neuronal metabolism and long-term memory across species. <i>Nature Metabolism</i>.
    2026;8(2):467-488. doi:<a href="https://doi.org/10.1038/s42255-026-01451-w">10.1038/s42255-026-01451-w</a>
  apa: Amrapali Vishwanath, A., Comyn, T., Mira, R. G., Brossier, C., Pascual-Caro,
    C., Faour, M., … de Juan-Sanz, J. (2026). Mitochondrial Ca2+ efflux controls neuronal
    metabolism and long-term memory across species. <i>Nature Metabolism</i>. Springer
    Nature. <a href="https://doi.org/10.1038/s42255-026-01451-w">https://doi.org/10.1038/s42255-026-01451-w</a>
  chicago: Amrapali Vishwanath, Anjali, Typhaine Comyn, Rodrigo G. Mira, Claire Brossier,
    Carlos Pascual-Caro, Maya Faour, Kahina Boumendil, et al. “Mitochondrial Ca2+
    Efflux Controls Neuronal Metabolism and Long-Term Memory across Species.” <i>Nature
    Metabolism</i>. Springer Nature, 2026. <a href="https://doi.org/10.1038/s42255-026-01451-w">https://doi.org/10.1038/s42255-026-01451-w</a>.
  ieee: A. Amrapali Vishwanath <i>et al.</i>, “Mitochondrial Ca2+ efflux controls
    neuronal metabolism and long-term memory across species,” <i>Nature Metabolism</i>,
    vol. 8, no. 2. Springer Nature, pp. 467–488, 2026.
  ista: Amrapali Vishwanath A, Comyn T, Mira RG, Brossier C, Pascual-Caro C, Faour
    M, Boumendil K, Chintaluri C, Ramon-Duaso C, Fan R, Ghosh K, Farrants H, Berwick
    J-P, Sivakumar R, Lopez-Manzaneda M, Schreiter ER, Preat T, Vogels TP, Rangaraju
    V, Busquets-Garcia A, Plaçais P-Y, Pavlowsky A, de Juan-Sanz J. 2026. Mitochondrial
    Ca2+ efflux controls neuronal metabolism and long-term memory across species.
    Nature Metabolism. 8(2), 467–488.
  mla: Amrapali Vishwanath, Anjali, et al. “Mitochondrial Ca2+ Efflux Controls Neuronal
    Metabolism and Long-Term Memory across Species.” <i>Nature Metabolism</i>, vol.
    8, no. 2, Springer Nature, 2026, pp. 467–88, doi:<a href="https://doi.org/10.1038/s42255-026-01451-w">10.1038/s42255-026-01451-w</a>.
  short: A. Amrapali Vishwanath, T. Comyn, R.G. Mira, C. Brossier, C. Pascual-Caro,
    M. Faour, K. Boumendil, C. Chintaluri, C. Ramon-Duaso, R. Fan, K. Ghosh, H. Farrants,
    J.-P. Berwick, R. Sivakumar, M. Lopez-Manzaneda, E.R. Schreiter, T. Preat, T.P.
    Vogels, V. Rangaraju, A. Busquets-Garcia, P.-Y. Plaçais, A. Pavlowsky, J. de Juan-Sanz,
    Nature Metabolism 8 (2026) 467–488.
date_created: 2026-03-02T10:04:49Z
date_published: 2026-02-11T00:00:00Z
date_updated: 2026-03-02T15:23:10Z
day: '11'
ddc:
- '570'
department:
- _id: TiVo
doi: 10.1038/s42255-026-01451-w
external_id:
  pmid:
  - '41673453'
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intvolume: '         8'
issue: '2'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: 467-488
pmid: 1
project:
- _id: c084a126-5a5b-11eb-8a69-d75314a70a87
  grant_number: 214316/Z/18/Z
  name: What’s in a memory? Spatiotemporal dynamics in strongly coupled recurrent
    neuronal networks.
publication: Nature Metabolism
publication_identifier:
  eissn:
  - 2522-5812
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Mitochondrial Ca2+ efflux controls neuronal metabolism and long-term memory
  across species
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 8
year: '2026'
...