Dataset Information

Specific post-translational modifications of VDAC3 in ALS-SOD1 model cells identified by High-Resolution Mass Spectrometry

ABSTRACT: Damage induced by oxidative stress is a key driver of the selective motor neuron death in amyotrophic lateral sclerosis (ALS). Mitochondria are among the main producers of ROS, but they also suffer particularly from their harmful effects. Voltage-dependent anion-selective channels (VDACs) are the most represented proteins of the outer mitochondrial membrane where they form pores controlling the permeation of metabolites responsible for mitochondrial functions. For these reasons, VDACs contribute to mitochondrial quality control and the entire energy metabolism of the cell. In this work we assessed whether oxidative stress in ALS induces post-translational modifications (PTMs) in VDAC3, a member of the VDAC family of outer mitochondrial membrane channel proteins, known for its role in redox signaling. At this end, protein samples enriched in VDACs were prepared from mitochondria of an ALS model cell line, NSC34 expressing human SOD1G93A, and analyzed by nUHPLC/High-Resolution nESI-MS/MS. Specific over-oxidation, deamidation, succination events were found in VDAC3 from ALS-related NSC34-SOD1G93A but not in non-ALS cell lines. We also report evidence that some PTMs may affect VDAC3 functionality. In particular, deamidation of Asn215 alone results in channel instability. Overall, our results suggest modifications of VDAC3 that can impact its protective role against ROS, which is particularly important in the ALS context.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Rosaria Saletti

LAB HEAD: Rosaria Saletti

PROVIDER: PXD036728 | Pride | 2023-03-11

REPOSITORIES: Pride

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			Action	DRS
	Raw_data_Biological_replicate_II_NSC-34.rar	Other
	Raw_data_Biological_replicate_I_NSC-34.rar	Other
	Search_Biological_Replicate_II_NSC-34.rar	Other
	Search_Biological_Replicate_I_NSC-34.rar	Other
	checksum.txt	Txt

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Specific Post-Translational Modifications of VDAC3 in ALS-SOD1 Model Cells Identified by High-Resolution Mass Spectrometry.

Pittalà Maria Gaetana Giovanna MGG Reina Simona S Nibali Stefano Conti SC Cucina Annamaria A Cubisino Salvatore Antonio Maria SAM Cunsolo Vincenzo V Amodeo Giuseppe Federico GF Foti Salvatore S De Pinto Vito V Saletti Rosaria R Messina Angela A

International journal of molecular sciences 20221213 24

Damage induced by oxidative stress is a key driver of the selective motor neuron death in amyotrophic lateral sclerosis (ALS). Mitochondria are among the main producers of ROS, but they also suffer particularly from their harmful effects. Voltage-dependent anion-selective channels (VDACs) are the most represented proteins of the outer mitochondrial membrane where they form pores controlling the permeation of metabolites responsible for mitochondrial functions. For these reasons, VDACs contribute ...[more]

PMID: 36555496

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