---
_id: '11551'
abstract:
- lang: eng
text: Imbalanced mitochondrial dNTP pools are known players in the pathogenesis
of multiple human diseases. Here we show that, even under physiological conditions,
dGTP is largely overrepresented among other dNTPs in mitochondria of mouse tissues
and human cultured cells. In addition, a vast majority of mitochondrial dGTP is
tightly bound to NDUFA10, an accessory subunit of complex I of the mitochondrial
respiratory chain. NDUFA10 shares a deoxyribonucleoside kinase (dNK) domain with
deoxyribonucleoside kinases in the nucleotide salvage pathway, though no specific
function beyond stabilizing the complex I holoenzyme has been described for this
subunit. We mutated the dNK domain of NDUFA10 in human HEK-293T cells while preserving
complex I assembly and activity. The NDUFA10E160A/R161A shows reduced dGTP binding
capacity in vitro and leads to a 50% reduction in mitochondrial dGTP content,
proving that most dGTP is directly bound to the dNK domain of NDUFA10. This interaction
may represent a hitherto unknown mechanism regulating mitochondrial dNTP availability
and linking oxidative metabolism to DNA maintenance.
acknowledgement: "We thank Dr, Luke Formosa (Department of Biochemistry and Molecular
Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia)
for his valuable advice and assistance on NDUFA10 molecular studies and Dr. Francesc
Canals and his team (Proteomics Laboratory, Vall d’Hebron Institute of Oncology
[VHIO], Universitat Autònoma de Barcelona, Barcelona, Spain) for their assistance
with LC-MS/MS analyses. This work was supported by the Spanish Ministry of Industry,
Economy and Competitiveness [grants BFU2014-52618-R, SAF2017-87506, and PID2020-112929RB-I00
to Y.C.], by the Spanish Instituto de Salud Carlos III [grants PI21/00554 and PMP15/00025
to R.M.], co-financed by the European Regional Development Fund (ERDF), and by an
NHMRC Project grant to M.R. (GNT1164459).\r\n"
article_number: '620'
article_processing_charge: No
author:
- first_name: David
full_name: Molina-Granada, David
last_name: Molina-Granada
- first_name: Emiliano
full_name: González-Vioque, Emiliano
last_name: González-Vioque
- first_name: Marris G.
full_name: Dibley, Marris G.
last_name: Dibley
- first_name: Raquel
full_name: Cabrera-Pérez, Raquel
last_name: Cabrera-Pérez
- first_name: Antoni
full_name: Vallbona-Garcia, Antoni
last_name: Vallbona-Garcia
- first_name: Javier
full_name: Torres-Torronteras, Javier
last_name: Torres-Torronteras
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
- first_name: Michael T.
full_name: Ryan, Michael T.
last_name: Ryan
- first_name: Yolanda
full_name: Cámara, Yolanda
last_name: Cámara
- first_name: Ramon
full_name: Martí, Ramon
last_name: Martí
citation:
ama: Molina-Granada D, González-Vioque E, Dibley MG, et al. Most mitochondrial dGTP
is tightly bound to respiratory complex I through the NDUFA10 subunit. Communications
Biology. 2022;5(1). doi:10.1038/s42003-022-03568-6
apa: Molina-Granada, D., González-Vioque, E., Dibley, M. G., Cabrera-Pérez, R.,
Vallbona-Garcia, A., Torres-Torronteras, J., … Martí, R. (2022). Most mitochondrial
dGTP is tightly bound to respiratory complex I through the NDUFA10 subunit. Communications
Biology. Springer Nature. https://doi.org/10.1038/s42003-022-03568-6
chicago: Molina-Granada, David, Emiliano González-Vioque, Marris G. Dibley, Raquel
Cabrera-Pérez, Antoni Vallbona-Garcia, Javier Torres-Torronteras, Leonid A Sazanov,
Michael T. Ryan, Yolanda Cámara, and Ramon Martí. “Most Mitochondrial DGTP Is
Tightly Bound to Respiratory Complex I through the NDUFA10 Subunit.” Communications
Biology. Springer Nature, 2022. https://doi.org/10.1038/s42003-022-03568-6.
ieee: D. Molina-Granada et al., “Most mitochondrial dGTP is tightly bound
to respiratory complex I through the NDUFA10 subunit,” Communications Biology,
vol. 5, no. 1. Springer Nature, 2022.
ista: Molina-Granada D, González-Vioque E, Dibley MG, Cabrera-Pérez R, Vallbona-Garcia
A, Torres-Torronteras J, Sazanov LA, Ryan MT, Cámara Y, Martí R. 2022. Most mitochondrial
dGTP is tightly bound to respiratory complex I through the NDUFA10 subunit. Communications
Biology. 5(1), 620.
mla: Molina-Granada, David, et al. “Most Mitochondrial DGTP Is Tightly Bound to
Respiratory Complex I through the NDUFA10 Subunit.” Communications Biology,
vol. 5, no. 1, 620, Springer Nature, 2022, doi:10.1038/s42003-022-03568-6.
short: D. Molina-Granada, E. González-Vioque, M.G. Dibley, R. Cabrera-Pérez, A.
Vallbona-Garcia, J. Torres-Torronteras, L.A. Sazanov, M.T. Ryan, Y. Cámara, R.
Martí, Communications Biology 5 (2022).
date_created: 2022-07-10T22:01:52Z
date_published: 2022-06-23T00:00:00Z
date_updated: 2023-08-03T11:51:58Z
day: '23'
ddc:
- '570'
department:
- _id: LeSa
doi: 10.1038/s42003-022-03568-6
external_id:
isi:
- '000815098500002'
pmid:
- ' 35739187'
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creator: kschuh
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date_updated: 2022-07-13T07:44:58Z
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language:
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month: '06'
oa: 1
oa_version: Published Version
pmid: 1
publication: Communications Biology
publication_identifier:
eissn:
- '23993642'
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Most mitochondrial dGTP is tightly bound to respiratory complex I through the
NDUFA10 subunit
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
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...