Maintaining a balanced and functional proteome homeostasis, or proteostasis, is critical for viability and development of all cells and organisms. Proteome requirements are constantly changing depending on differentiation and development stages and because of insurgency of acute or chronic stress, as in case of alteration of temperature, redox status, pH, nutrients availability, viral infection, mutations, cancer and aging. Proteostasis unbalance can cause overwhelming protein misfolding and aggregation eventually leading to cell death. Cells are equipped with a complex signaling network of pathways involved in biogenesis, folding, trafficking and degradation of proteins, that ensure that proteomic equilibrium is preserved in each cell compartment in physiological states by utilizing a plethora of signaling factors, as well as transcriptional and translational programs. Accumulation of misfolded proteins triggers a series of stress responses, specific for each cellular compartment in which it occurs: responses to unfolded proteins are activated in the cytosol (heat shock response, HSR), in the ER (unfolded protein response, UPR) and in mitochondria (UPRmt) and these are in addition deeply connected to the oxidative stress response, the ubiquitin-proteasome system (UPS) and autophagy.
Proteome homeostasis is associated with stem cell identity in mammalian pluripotent stem cells: whereas immortal multipotent stem cells exhibit a great capacity to maintain proteostasis, aging somatic stem cells lose it. Proteostasis variations and the ensuing responses play a main role in many physiological processes like differentiation and aging and in different pathologies, as diverse as neurodegenerative diseases, diabetes, cardiac ischemia/reperfusion injury, cystic fibrosis and cancer. For example, abnormal accumulation of aggregated proteins is associated with Alzheimer’s and Parkinson’s disease. The elevated capacity of adapting to changes in proteome requirements favors survival and proliferation of cancer cells, challenged with redox unbalance and expression of mutant proteins, and protects from the effects of chemotherapeutic agents. Therefore, a deep knowledge of the proteostasis network it is of utmost importance to find specific molecular targets to increase or decrease cell viability, for example to hinder neurodegenerative processes or to increase the efficacy of cancer treatments.
The aim of the current Research Topic is to welcome studies reporting the latest findings on the pathways involved in the proteostasis network. Articles relative to the cellular, molecular, biochemical, structural, and physiological mechanisms underlying proteome homeostasis involving the cytosolic, ER and mitochondria compartments, as well as those regarding therapeutic strategies targeting such mechanisms are welcome. The research can concern physiological and pathological conditions including development and differentiation, cancer, neurodegeneration, inflammation, and aging.
Areas to be covered in the current Research Topic may include, but are not limited to:
- Stress responses of cytosol, ER and mitochondria preserving proteome homeostasis;
- Roles of protein degradation systems (lysosomal system, UPS and autophagy), in maintaining proteostasis;
- Role of redox homeostasis and of the oxidative stress response in regulating proteome homeostasis;
- Therapeutic strategies targeting the proteostasis network;
- Methods to investigate the proteostasis network.
Maintaining a balanced and functional proteome homeostasis, or proteostasis, is critical for viability and development of all cells and organisms. Proteome requirements are constantly changing depending on differentiation and development stages and because of insurgency of acute or chronic stress, as in case of alteration of temperature, redox status, pH, nutrients availability, viral infection, mutations, cancer and aging. Proteostasis unbalance can cause overwhelming protein misfolding and aggregation eventually leading to cell death. Cells are equipped with a complex signaling network of pathways involved in biogenesis, folding, trafficking and degradation of proteins, that ensure that proteomic equilibrium is preserved in each cell compartment in physiological states by utilizing a plethora of signaling factors, as well as transcriptional and translational programs. Accumulation of misfolded proteins triggers a series of stress responses, specific for each cellular compartment in which it occurs: responses to unfolded proteins are activated in the cytosol (heat shock response, HSR), in the ER (unfolded protein response, UPR) and in mitochondria (UPRmt) and these are in addition deeply connected to the oxidative stress response, the ubiquitin-proteasome system (UPS) and autophagy.
Proteome homeostasis is associated with stem cell identity in mammalian pluripotent stem cells: whereas immortal multipotent stem cells exhibit a great capacity to maintain proteostasis, aging somatic stem cells lose it. Proteostasis variations and the ensuing responses play a main role in many physiological processes like differentiation and aging and in different pathologies, as diverse as neurodegenerative diseases, diabetes, cardiac ischemia/reperfusion injury, cystic fibrosis and cancer. For example, abnormal accumulation of aggregated proteins is associated with Alzheimer’s and Parkinson’s disease. The elevated capacity of adapting to changes in proteome requirements favors survival and proliferation of cancer cells, challenged with redox unbalance and expression of mutant proteins, and protects from the effects of chemotherapeutic agents. Therefore, a deep knowledge of the proteostasis network it is of utmost importance to find specific molecular targets to increase or decrease cell viability, for example to hinder neurodegenerative processes or to increase the efficacy of cancer treatments.
The aim of the current Research Topic is to welcome studies reporting the latest findings on the pathways involved in the proteostasis network. Articles relative to the cellular, molecular, biochemical, structural, and physiological mechanisms underlying proteome homeostasis involving the cytosolic, ER and mitochondria compartments, as well as those regarding therapeutic strategies targeting such mechanisms are welcome. The research can concern physiological and pathological conditions including development and differentiation, cancer, neurodegeneration, inflammation, and aging.
Areas to be covered in the current Research Topic may include, but are not limited to:
- Stress responses of cytosol, ER and mitochondria preserving proteome homeostasis;
- Roles of protein degradation systems (lysosomal system, UPS and autophagy), in maintaining proteostasis;
- Role of redox homeostasis and of the oxidative stress response in regulating proteome homeostasis;
- Therapeutic strategies targeting the proteostasis network;
- Methods to investigate the proteostasis network.
