Constitutive activation of AMP-activated protein kinase (AMPK) propel mitochondrial biogenesis

摘要

Mitochondrial biogenesis is primarily a critical adaptation aimed to balance an increased workload in an attempt to maintain appropriate body perfusion. Until recently, the signaling mechanisms responsible for this response are poorly understood. To examine the role of AMP-activated protein kinase (AMPK), an evolutionarily conserved fuel sensor, in mitochondrial biogenesis, we used constitutively active and antisense inhibition genetic tools in Dictyostelium discoideum. Constitutive activation of AMPK culminated in mitochondrial proliferation and elevated ATP generation; this became marked with higher plasmid copies. Antisense inhibition of AMPK yielded non–significant decrease in the mitochondrial content at low levels. However, the more severe the antisense inhibition, the more significant the diminution of AMPK function, resulting in the more apparent decrease in the Advanced Technology Program (ATP) and mitotracker fluorescence. This finding provides direct genetic evidence that AMPK plays a significant role in ameliorating the effects of cellular energy deficit through mitochondrial proliferation. Thus, the constitutive activation of AMPK initiates signalling to downstream targets. The result perturbation of these pathways would culminate in the mitochondrial biogenesis. Taken together, these findings show the constitutive activation of AMPK propels in vivo mitochondrial biogenesis and ATP generation in D. discoideum as in other organisms.