In this work, by combining HRMS analysis with “in-solution” digestion of an enriched fraction of VDACs, in VDAC3 purified from NSC34-SOD1G93A model ALS-SOD1 cells, we identified specific irreversible PTMs that can destabilize the channel by impacting its function. This evidence concerns the gene SOD1 and amyotrophic lateral sclerosis.