Fig. 3.

Intrinsic connections between redox homeostasis and proteostasis, and the role of cold atmospheric plasma (CAP) as a possible proteostasis regulator. Heat shock protein 90 (HSP90) is distributed in the cytoplasm, endoplasmic reticulum (ER), mitochondria, cell membrane, and extracellular space. Take cytoplasm as the example, disturbed redox level homeostasis induces abnormal formation of intra- and inter-molecular disulfide bonds of proteins, leading to abnormal protein folding. An increased level of misfolded proteins results in protein degradation burden. On the other hand, intact HSP90 keeps the stabilization of proteins including some abnormally folded ones, leading to disturbed proteostasis. Failed proteostasis acts as a harmful stimulus to trigger inflammation as manifested as the release of pro-inflammatory cytokines. These cytokines in turn further aggregate redox imbalance, and drive the pathogenesis of diseases such as cancers and autoimmune diseases. CAP can possibly regulate proteostasis by inducing reactive oxygen species (ROS)-dependent HSP90 cleavage, leading to the degradation of abnormally folded proteins and returned proteostasis.