Figure 3.

S-Nitrosylation and S-Glutathionylation roles in mitochondria redox-metabolism interplay. The targets of S-glutathionylation in the TCA cycle are PDH, ACN, IDH, KGDH, SDT and MDH. The S-glutathionylation of TCA cycle enzymes protects them from irreversible oxidation until the redox status is impaired and inhibits ROS production and electrons transfer to the ETC to further minimize the ROS levels under oxidative stress. Complex I and V inhibitions by S-glutathionylation share similar purposes with the S-glutathionylation of TCA cycle enzymes and ultimately minimize ROS production. Only Complex II S-glutathionylation has been shown to be integral for its constitutive activity. Under excessive ROS, the glutathionylation of ANT and VDAC prevents the formation of MPTP in inhibiting apoptosis, whereas UCP glutathionylation increases ROS formations. The targets of S-nitrosylation in the TCA cycle are ACN, KGDH and SDH, which in turn inhibits their function to minimize ROS. All mitochondria Complexes I-V can be nitrosylated under increased oxidative/nitrosative stress both to minimize ROS production and to scavenge NO. Under basal NO levels, the S-nitrosylation of VDAC and MPTP constituents inhibits their functions in providing protection from apoptosis, whereas under excessive NO levels, aberrant S-nitrosylation activates VDAC-mediated cytochrome c release and apoptosis or/and CYPD S-nitrosylation, the activation of MPTP, the ablation of ATP production and necrosis (OMM: outer mitochondrial membrane; IMM: inner mitochondrial membrane). Created with BioRender.com.