Fig. 5

Role of ROS in regulating mitophagy in OP. Age and estrogen deficiency cause enhanced reactive oxygen species (ROS) generation in MSCs. ROS lead to mitochondrial dysfunction accompanied by a reduced mitochondrial membrane potential (ΔΨm). Subsequent PINK1 accumulation at the outer surface of the mitochondrial membrane initiates mitophagy by recruitment of Parkin that promotes ubiquitination (green dots) of OMM proteins (OMMP). Ubiquitinated proteins bind directly or indirectly to autophagy receptor LC3 via p62 on mitophagosomes. Aberrant mitophagy may result in increased apoptosis, promoting marrow adipogenesis as well as suppressing osteogenesis, all consequently contributing to OP development