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A Proteomic Study of the Dual Oncogenic and Tumor-Suppressive Roles of SIRT3 in Lung and Breast Cancer Cell Lines

Ayala Reyes, Marisol LU ; Fernández Coto, Diana Lashidua LU ; Alonso Bastida, Ramiro LU ; Marko-Varga, György LU ; Gil, Jeovanis LU orcid and Encarnación-Guevara, Sergio (2026) In International Journal of Molecular Sciences 27(3).
Abstract

Mitochondria play a crucial role in metabolism and energy production by generating adenosine triphosphate (ATP) through oxidative phosphorylation. They also help maintain intracellular calcium levels, facilitate communication between the nucleus and cytoplasm, detoxify reactive oxygen species (ROS), and regulate apoptosis. Reversible acetylation of mitochondrial proteins is a key post-translational modification influencing these processes, with the NAD+-dependent deacetylase SIRT3 being a major regulator. While SIRT3 has been described as a tumor suppressor in some contexts and as a tumor promoter in others, its role appears to be tissue- and metabolism-specific. Here, we compared the proteomic and acetylomic responses of... (More)

Mitochondria play a crucial role in metabolism and energy production by generating adenosine triphosphate (ATP) through oxidative phosphorylation. They also help maintain intracellular calcium levels, facilitate communication between the nucleus and cytoplasm, detoxify reactive oxygen species (ROS), and regulate apoptosis. Reversible acetylation of mitochondrial proteins is a key post-translational modification influencing these processes, with the NAD+-dependent deacetylase SIRT3 being a major regulator. While SIRT3 has been described as a tumor suppressor in some contexts and as a tumor promoter in others, its role appears to be tissue- and metabolism-specific. Here, we compared the proteomic and acetylomic responses of lung adenocarcinoma (A549) and breast adenocarcinoma (MCF7) cell lines to SIRT3 inhibition by 3-TYP. The two lines were selected based on distinct metabolic phenotypes and reported differences in basal SIRT3 abundance. Total proteome and mitochondrial-enriched fractions were analyzed separately for each cell line to avoid cross-line normalization bias. We identified 6457 proteins and 4199 acetylated peptides, revealing distinct pathway enrichments and acetylation changes after SIRT3 inhibition. A549 cells showed increased oxidative metabolism, while MCF7 cells exhibited metabolic reprogramming. These results indicate that the proteomic impact of SIRT3 modulation is strongly influenced by cellular metabolic context. All raw mass spectrometry data are publicly available in PXD063181.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
acetylation, cancer, metabolism, mitochondria, oxidative phosphorylation, post-translational modification, sirtuin
in
International Journal of Molecular Sciences
volume
27
issue
3
article number
1325
publisher
MDPI AG
external identifiers
  • pmid:41683751
  • scopus:105030042821
ISSN
1661-6596
DOI
10.3390/ijms27031325
language
English
LU publication?
yes
id
8f343af8-ff7c-401f-a00b-50c4bb298b79
date added to LUP
2026-03-03 15:12:25
date last changed
2026-05-27 03:45:27
@article{8f343af8-ff7c-401f-a00b-50c4bb298b79,
  abstract     = {{<p>Mitochondria play a crucial role in metabolism and energy production by generating adenosine triphosphate (ATP) through oxidative phosphorylation. They also help maintain intracellular calcium levels, facilitate communication between the nucleus and cytoplasm, detoxify reactive oxygen species (ROS), and regulate apoptosis. Reversible acetylation of mitochondrial proteins is a key post-translational modification influencing these processes, with the NAD<sup>+</sup>-dependent deacetylase SIRT3 being a major regulator. While SIRT3 has been described as a tumor suppressor in some contexts and as a tumor promoter in others, its role appears to be tissue- and metabolism-specific. Here, we compared the proteomic and acetylomic responses of lung adenocarcinoma (A549) and breast adenocarcinoma (MCF7) cell lines to SIRT3 inhibition by 3-TYP. The two lines were selected based on distinct metabolic phenotypes and reported differences in basal SIRT3 abundance. Total proteome and mitochondrial-enriched fractions were analyzed separately for each cell line to avoid cross-line normalization bias. We identified 6457 proteins and 4199 acetylated peptides, revealing distinct pathway enrichments and acetylation changes after SIRT3 inhibition. A549 cells showed increased oxidative metabolism, while MCF7 cells exhibited metabolic reprogramming. These results indicate that the proteomic impact of SIRT3 modulation is strongly influenced by cellular metabolic context. All raw mass spectrometry data are publicly available in PXD063181.</p>}},
  author       = {{Ayala Reyes, Marisol and Fernández Coto, Diana Lashidua and Alonso Bastida, Ramiro and Marko-Varga, György and Gil, Jeovanis and Encarnación-Guevara, Sergio}},
  issn         = {{1661-6596}},
  keywords     = {{acetylation; cancer; metabolism; mitochondria; oxidative phosphorylation; post-translational modification; sirtuin}},
  language     = {{eng}},
  number       = {{3}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  title        = {{A Proteomic Study of the Dual Oncogenic and Tumor-Suppressive Roles of SIRT3 in Lung and Breast Cancer Cell Lines}},
  url          = {{http://dx.doi.org/10.3390/ijms27031325}},
  doi          = {{10.3390/ijms27031325}},
  volume       = {{27}},
  year         = {{2026}},
}