Mitochondrial flash(mitoflash)is the electrochemical excitation of a single mitochondrion and plays diverse signaling roles in a variety of cells.From the viewpoint of bioenergetics,it represents the transient uncoupl...Mitochondrial flash(mitoflash)is the electrochemical excitation of a single mitochondrion and plays diverse signaling roles in a variety of cells.From the viewpoint of bioenergetics,it represents the transient uncoupling of mitochondrial respiration from ATP synthesis.Brown adipose tissue(BAT)produces heat,primarily via mitochondrial uncoupled respiration.Here,we aim to illustrate the mitoflash activity in BAT thermogenesis.We show that BAT mitochondria undergo stochastic and intermittent mitoflashes at the levels of isolated mitochondria,cultured brown adipocytes,and even intact BAT.A BAT mitoflash contains multiple signals,including transient depolarization of mitochondrial membrane potential,transient matrix alkalization,and bursting production of reactive oxygen species.Importantly,thermogenic activation by b3-adrenergic stimulation dramatically augments mitoflash incidence,with mild effects on its unitary characteristics.Ablation of the thermogenic uncoupling protein 1(UCP1)showed little effect on mitoflash biogenesis during heat production.Collectively,our results suggest that mitoflash might constitute an elemental signaling activity of mitochondria to regulate BAT thermogenesis.展开更多
基金supported by the National Natural Science Foundation of China(31971158,92157105,and 32293210)the National Science and Technology Innovation 2030Major Program(2022ZD0211900)CAMS Innovation Fund for Medical Sciences(2019-I2M-5–054).
文摘Mitochondrial flash(mitoflash)is the electrochemical excitation of a single mitochondrion and plays diverse signaling roles in a variety of cells.From the viewpoint of bioenergetics,it represents the transient uncoupling of mitochondrial respiration from ATP synthesis.Brown adipose tissue(BAT)produces heat,primarily via mitochondrial uncoupled respiration.Here,we aim to illustrate the mitoflash activity in BAT thermogenesis.We show that BAT mitochondria undergo stochastic and intermittent mitoflashes at the levels of isolated mitochondria,cultured brown adipocytes,and even intact BAT.A BAT mitoflash contains multiple signals,including transient depolarization of mitochondrial membrane potential,transient matrix alkalization,and bursting production of reactive oxygen species.Importantly,thermogenic activation by b3-adrenergic stimulation dramatically augments mitoflash incidence,with mild effects on its unitary characteristics.Ablation of the thermogenic uncoupling protein 1(UCP1)showed little effect on mitoflash biogenesis during heat production.Collectively,our results suggest that mitoflash might constitute an elemental signaling activity of mitochondria to regulate BAT thermogenesis.
