Abstract
Cysteine residues are reactive amino acids that can undergo several modifications driven by redox reagents. Mitochondria are the source of an abundant production of radical species, and it is surprising that such a large availability of highly reactive chemicals is compatible with viable and active organelles, needed for the cell functions. In this work, we review the results highlighting the modifications of cysteines in the most abundant proteins of the outer mitochondrial membrane (OMM), that is, the voltage-dependent anion selective channel (VDAC) isoforms. This interesting protein family carries several cysteines exposed to the oxidative intermembrane space (IMS). Through mass spectrometry (MS) analysis, cysteine posttranslational modifications (PTMs) were precisely determined, and it was discovered that such cysteines can be subject to several oxidization degrees, ranging from the disulfide bridge to the most oxidized, the sulfonic acid, one. The large spectra of VDAC cysteine oxidations, which is unique for OMM proteins, indicate that they have both a regulative function and a buffering capacity able to counteract excess of mitochondrial reactive oxygen species (ROS) load. The consequence of these peculiar cysteine PTMs is discussed.
Highlights
Simona Reina1*, Maria Gaetana Giovanna Pittalà2, Francesca Guarino2, Angela Messina1, Vito De Pinto2, Salvatore Foti3 and Rosaria Saletti3
We review the results highlighting the modifications of cysteines in the most abundant proteins of the outer mitochondrial membrane (OMM), that is, the voltagedependent anion selective channel (VDAC) isoforms
The reasons for this inconsistency reside both in the molecular mechanisms that allow a single gene to encode for numerous proteins and in the posttranslational modifications (PTMs) which represent a wide range of chemical changes that proteins may undergo after synthesis
Summary
Cysteine residues constitute only 2% of the total amino acid content, but the mitochondrial proteome is rich in protein thiols. It has been reported that the sulfenylation of the Cys253 residue of uncoupling protein 1 (UCP1) within the brown adipose mitochondria of mammalian cells participates in the thermogenic regulation of energy expenditure (Chouchani et al, 2016). The selective S-nitrosation of the Cys residue on the ND3 subunit of CI was instead proposed to be cardioprotective (Chouchani et al, 2013). ROS can oxidatively damage biomolecules (proteins, DNA, and lipids), leading to neurological disorders, metabolic diseases, aging (Bulteau et al, 2006), and other pathologies. The control of the cellular ROS balance mainly relies on two redox regulatory systems: the reduced/oxidized thioredoxin and the glutathione (GSH)/glutathione disulfide (GSSG) (Holmgren et al, 2005; Jones, 2006)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
