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Dynamics of Mitochondrial Proteome and Acetylome in Glioblastoma Cells with Contrasting Metabolic Phenotypes

Fernández-Coto, Diana Lashidua ; Gil, Jeovanis LU ; Ayala, Guadalupe and Encarnación-Guevara, Sergio (2024) In International Journal of Molecular Sciences 25(6).
Abstract

Glioblastoma, a type of cancer affecting the central nervous system, is characterized by its poor prognosis and the dynamic alteration of its metabolic phenotype to fuel development and progression. Critical to cellular metabolism, mitochondria play a pivotal role, where the acetylation of lysine residues on mitochondrial enzymes emerges as a crucial regulatory mechanism of protein function. This post-translational modification, which negatively impacts the mitochondrial proteome’s functionality, is modulated by the enzyme sirtuin 3 (SIRT3). Aiming to elucidate the regulatory role of SIRT3 in mitochondrial metabolism within glioblastoma, we employed high-resolution mass spectrometry to analyze the proteome and acetylome of two... (More)

Glioblastoma, a type of cancer affecting the central nervous system, is characterized by its poor prognosis and the dynamic alteration of its metabolic phenotype to fuel development and progression. Critical to cellular metabolism, mitochondria play a pivotal role, where the acetylation of lysine residues on mitochondrial enzymes emerges as a crucial regulatory mechanism of protein function. This post-translational modification, which negatively impacts the mitochondrial proteome’s functionality, is modulated by the enzyme sirtuin 3 (SIRT3). Aiming to elucidate the regulatory role of SIRT3 in mitochondrial metabolism within glioblastoma, we employed high-resolution mass spectrometry to analyze the proteome and acetylome of two glioblastoma cell lines, each exhibiting distinct metabolic behaviors, following the chemical inhibition of SIRT3. Our findings reveal that the protein synthesis machinery, regulated by lysine acetylation, significantly influences the metabolic phenotype of these cells. Moreover, we have shed light on potential novel SIRT3 targets, thereby unveiling new avenues for future investigations. This research highlights the critical function of SIRT3 in mitochondrial metabolism and its broader implications for cellular energetics. It also provides a comparative analysis of the proteome and acetylome across glioblastoma cell lines with opposing metabolic phenotypes.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
glioblastoma, lysine acetylation, metabolism, mitochondria, SIRT3
in
International Journal of Molecular Sciences
volume
25
issue
6
article number
3450
publisher
MDPI AG
external identifiers
  • pmid:38542426
  • scopus:85189106961
ISSN
1661-6596
DOI
10.3390/ijms25063450
language
English
LU publication?
yes
id
39399c75-4fd3-48af-85a2-2fa337d991b1
date added to LUP
2024-04-18 14:58:41
date last changed
2024-04-19 03:00:03
@article{39399c75-4fd3-48af-85a2-2fa337d991b1,
  abstract     = {{<p>Glioblastoma, a type of cancer affecting the central nervous system, is characterized by its poor prognosis and the dynamic alteration of its metabolic phenotype to fuel development and progression. Critical to cellular metabolism, mitochondria play a pivotal role, where the acetylation of lysine residues on mitochondrial enzymes emerges as a crucial regulatory mechanism of protein function. This post-translational modification, which negatively impacts the mitochondrial proteome’s functionality, is modulated by the enzyme sirtuin 3 (SIRT3). Aiming to elucidate the regulatory role of SIRT3 in mitochondrial metabolism within glioblastoma, we employed high-resolution mass spectrometry to analyze the proteome and acetylome of two glioblastoma cell lines, each exhibiting distinct metabolic behaviors, following the chemical inhibition of SIRT3. Our findings reveal that the protein synthesis machinery, regulated by lysine acetylation, significantly influences the metabolic phenotype of these cells. Moreover, we have shed light on potential novel SIRT3 targets, thereby unveiling new avenues for future investigations. This research highlights the critical function of SIRT3 in mitochondrial metabolism and its broader implications for cellular energetics. It also provides a comparative analysis of the proteome and acetylome across glioblastoma cell lines with opposing metabolic phenotypes.</p>}},
  author       = {{Fernández-Coto, Diana Lashidua and Gil, Jeovanis and Ayala, Guadalupe and Encarnación-Guevara, Sergio}},
  issn         = {{1661-6596}},
  keywords     = {{glioblastoma; lysine acetylation; metabolism; mitochondria; SIRT3}},
  language     = {{eng}},
  number       = {{6}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  title        = {{Dynamics of Mitochondrial Proteome and Acetylome in Glioblastoma Cells with Contrasting Metabolic Phenotypes}},
  url          = {{http://dx.doi.org/10.3390/ijms25063450}},
  doi          = {{10.3390/ijms25063450}},
  volume       = {{25}},
  year         = {{2024}},
}