Roles of mitochondrial unfolded protein response in mammalian stem cells

The mitochondrial unfolded protein response(UPRmt)is an evolutionarily conserved adaptive mechanism for improving cell survival under mitochondrial stress.Under physiological and pathological conditions,the UPRmt is the key to maintaining intracellular homeostasis and proteostasis.Important roles of the UPRmt have been demonstrated in a variety of cell types and in cell development,metabolism,and immune processes.UPRmt dysfunction leads to a variety of pathologies,including cancer,inflammation,neurodegenerative disease,metabolic disease,and immune disease.Stem cells have a special ability to selfrenew and differentiate into a variety of somatic cells and have been shown to exist in a variety of tissues.These cells are involved in development,tissue renewal,and some disease processes.Although the roles and regulatory mechanisms of the UPRmt in somatic cells have been widely reported,the roles of the UPRmt in stem cells are not fully understood.The roles and functions of the UPRmt depend on stem cell type.Therefore,this paper summarizes the potential significance of the UPRmt in embryonic stem cells,tissue stem cells,tumor stem cells,and induced pluripotent stem cells.The purpose of this review is to provide new insights into stem cell differentiation and tumor pathogenesis.

Nrf2-mediated ferroptosis of spermatogenic cells involved in male reproductive toxicity induced by polystyrene nanoplastics in mice

Microplastics(MPs)and nanoplastics(NPs)have become hazardous materials due to the massive amount of plastic waste and disposable masks,but their specific health effects remain uncertain.In this study,fluorescence-labeled polystyrene NPs(PS-NPs)were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in vivo.Interestingly,whole-body imaging found that PS-NPs accumulated in the testes of mice.Therefore,the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice,and their mechanisms,were investigated.After oral exposure to PS-NPs,their spermatogenesis was affected and the spermatogenic cells were damaged.The spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing(RNA-seq)to determine the toxic mechanisms;a ferroptosis pathway was found after PS-NP exposure.The phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1(Fer-1),and it was also found that nuclear factor erythroid 2-related factor 2(Nrf2)played an important role in spermatogenic cell ferroptosis induced by PS-NPs.Finally,it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive toxicity.This study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.