Abstract
Cardiovascular disorder is the major health burden and cause of death among individuals worldwide. As the cardiomyocytes lack the ability for self-renewal, it is utmost necessary to surveil the protein quality in the cells. The Bcl-2 associated anthanogene protein (BAG) family and molecular chaperones (HSP70, HSP90) actively participate in maintaining cellular protein quality control (PQC) to limit cellular dysfunction in the cells. The BAG family contains a unique BAG domain which facilitates their interaction with the ATPase domain of the heat shock protein 70 (HSP70) to assist in protein folding. Among the BAG family members (BAG1-6), BAG5 protein is unique since it has five domains in tandem, and the binding of BD5 induces certain conformational changes in the nucleotide-binding domain (NBD) of HSP70 such that it loses its affinity for binding to ADP and results in enhanced protein refolding activity of HSP70. In this review, we shall describe the role of BAG5 in modulating mitophagy, endoplasmic stress, and cellular viability. Also, we have highlighted the interaction of BAG5 with other proteins, including PINK, DJ-1, CHIP, and their role in cellular PQC. Apart from this, we have described the role of BAG5 in cellular metabolism and aging.
Highlights
Cardiovascular diseases (CVDs), including ischemic heart disease, heart failure, or other vascular conditions, constitute the leading cause of mortality among individuals worldwide (Pinto et al, 2021; Virani et al, 2021)
It is believed that aging is the most significant risk factor associated with CVDs, neurological disorders, inflammation, metabolic abnormality, and drug toxicity which causes premature death worldwide
It was noticed that dysregulation of cellular proteostasis could cause formation of cellular protein aggregates, which can lead to the development of CVDs and neurological disorders
Summary
Cardiovascular diseases (CVDs), including ischemic heart disease, heart failure, or other vascular conditions, constitute the leading cause of mortality among individuals worldwide (Pinto et al, 2021; Virani et al, 2021). The cell uses a vesicle-mediated protein degradation system called autophagy to degrade cellular proteins and subcellular organelles (Delbridge et al, 2017). Impairment of cellular PQC and accumulation of protein aggregates with faulty subcellular organelles leads to the generation of oxidative stress, inflammation, and cell death (Li et al, 2021). These modifications are known to be associated with the impairment of several organ functions and the development of several life-threatening diseases including, CVD, neurological disorders, and premature aging (Gong et al, 2016; Kaur et al, 2020). This review will discuss the evolving role of co-chaperone Bcl-2 associated anthanogene protein (BAG5) in UPS, autophagy, mitophagy, oxidative stress, metabolism, and its association with CVDs, Alzheimer’s disease, and Parkinson’s disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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
