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Review

VDACs Post-Translational Modifications Discovery by Mass Spectrometry: Impact on Their Hub Function

by
Maria Gaetana Giovanna Pittalà
1,
Stefano Conti Nibali
2,
Simona Reina
2,
Vincenzo Cunsolo
3,
Antonella Di Francesco
3,
Vito De Pinto
2,
Angela Messina
1,
Salvatore Foti
3 and
Rosaria Saletti
3,*
1
Molecular Biology Laboratory, Department of Biological, Geological and Environmental Sciences, University of Catania, Via S. Sofia 64, 95123 Catania, Italy
2
Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 64, 95123 Catania, Italy
3
Organic Mass Spectrometry Laboratory, Department of Chemical Sciences, University of Catania, Via S. Sofia 64, 95123 Catania, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(23), 12833; https://doi.org/10.3390/ijms222312833
Submission received: 25 October 2021 / Revised: 12 November 2021 / Accepted: 23 November 2021 / Published: 27 November 2021
(This article belongs to the Special Issue VDAC as a Cellular Hub: Docking Molecules and Interactions)

Abstract

VDAC (voltage-dependent anion selective channel) proteins, also known as mitochondrial porins, are the most abundant proteins of the outer mitochondrial membrane (OMM), where they play a vital role in various cellular processes, in the regulation of metabolism, and in survival pathways. There is increasing consensus about their function as a cellular hub, connecting bioenergetics functions to the rest of the cell. The structural characterization of VDACs presents challenging issues due to their very high hydrophobicity, low solubility, the difficulty to separate them from other mitochondrial proteins of similar hydrophobicity and the practical impossibility to isolate each single isoform. Consequently, it is necessary to analyze them as components of a relatively complex mixture. Due to the experimental difficulties in their structural characterization, post-translational modifications (PTMs) of VDAC proteins represent a little explored field. Only in recent years, the increasing number of tools aimed at identifying and quantifying PTMs has allowed to increase our knowledge in this field and in the mechanisms that regulate functions and interactions of mitochondrial porins. In particular, the development of nano-reversed phase ultra-high performance liquid chromatography (nanoRP-UHPLC) and ultra-sensitive high-resolution mass spectrometry (HRMS) methods has played a key role in this field. The findings obtained on VDAC PTMs using such methodologies, which permitted an in-depth characterization of these very hydrophobic trans-membrane pore proteins, are summarized in this review.
Keywords: voltage dependent anion channel; cysteine overoxidation; deamidation; hydroxyapatite; high-resolution mass spectrometry; post-translational modifications voltage dependent anion channel; cysteine overoxidation; deamidation; hydroxyapatite; high-resolution mass spectrometry; post-translational modifications

Share and Cite

MDPI and ACS Style

Pittalà, M.G.G.; Conti Nibali, S.; Reina, S.; Cunsolo, V.; Di Francesco, A.; De Pinto, V.; Messina, A.; Foti, S.; Saletti, R. VDACs Post-Translational Modifications Discovery by Mass Spectrometry: Impact on Their Hub Function. Int. J. Mol. Sci. 2021, 22, 12833. https://doi.org/10.3390/ijms222312833

AMA Style

Pittalà MGG, Conti Nibali S, Reina S, Cunsolo V, Di Francesco A, De Pinto V, Messina A, Foti S, Saletti R. VDACs Post-Translational Modifications Discovery by Mass Spectrometry: Impact on Their Hub Function. International Journal of Molecular Sciences. 2021; 22(23):12833. https://doi.org/10.3390/ijms222312833

Chicago/Turabian Style

Pittalà, Maria Gaetana Giovanna, Stefano Conti Nibali, Simona Reina, Vincenzo Cunsolo, Antonella Di Francesco, Vito De Pinto, Angela Messina, Salvatore Foti, and Rosaria Saletti. 2021. "VDACs Post-Translational Modifications Discovery by Mass Spectrometry: Impact on Their Hub Function" International Journal of Molecular Sciences 22, no. 23: 12833. https://doi.org/10.3390/ijms222312833

APA Style

Pittalà, M. G. G., Conti Nibali, S., Reina, S., Cunsolo, V., Di Francesco, A., De Pinto, V., Messina, A., Foti, S., & Saletti, R. (2021). VDACs Post-Translational Modifications Discovery by Mass Spectrometry: Impact on Their Hub Function. International Journal of Molecular Sciences, 22(23), 12833. https://doi.org/10.3390/ijms222312833

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