PURPOSE: To investigate the mechanism of PHB1 on F0F1-ATPase and its effect on exercise capacity,and whether PHB1 can be used as a scientific basis for regulating energy metabolism. METHODS: An animal model of moderate-intensity exercise and exhaustive exercise and a complete C2C12 cell line culture system,PHB1 overexpression and RNA interference in adenovirus vectors were established.32 8-week-old healthy male SD rats were randomly divided into three groups: normal control(NC),moderate intensity exercise(MIE)and acute exhaustive exercise(AEE)groups.NC and AEE:routinely raised. MIE:Rats were run at 15m/min per day for 60min until the end of the 8th week.Slope:10%.AEE:The rats were subjected to acute exhaustive exercise after 8 weeks.They were sacrificed 48h after the last experiment.PHB1 expression,ATP content,FOF1-ATPase,oxidative stress (ROS),cellular oxygen consumption rate (OCR),and mitochondrial respiratory function(RCR)in skeletal muscle were measured by animal and cell experiments. RESULTS: Compared with NC,MIE group RCR(+73%,p<0.001),ATP content (+48%,p<0.05),FOF1-ATPase activity(+79%,p<0.05),PHB1 expression(+42%,p<0.01),ROS level(-75%,p<0.001)decreased;AEE group RCR(-58%,p<0.05),ATP content (-55%,p<0.05),FOF1-ATPase activity(-56%,p<0.001),PHB1 expression(-31%,p<0.01)decreased,and ROS(+79%,p<0.05)increased.In C2C12 cells,PHB1 overexpression group,ATP content(+86%,p<0.01),FOF1-ATPase mRNA level(+59%,p<0.05),FOF1-ATPase protein expression level(+69%,p<0.05),FOF1-ATPase activity(+226%, p<0.01),and OCR(+256%,p<0.01),ROS level(-74%,p<0.01),significant enhancement of cellular respiratory function.In the low expression group of PHB1,ATP content(-21%,p<0.01),FOF1-ATPase mRNA level(-64%, p<0.05),FOF1-ATPase protein expression level(-89%,p<0.05),FOF1-ATPase activity(-93%,p<0.01),and OCR(-190%,p<0.01),ROS production was significantly increased(+104%,p<0.01),and cellular respiratory function was significantly reduced. CONCLUSION: In energy metabolism,PHB1 may play a role in stabilizing the mitochondrial structure and positively regulating FOF1-ATPase activity,thereby enhance mitochondrial function and promoting energy metabolism.Supported by NSFC(No.31470061)