AMPK Localization: A Key to Differential Energy Regulation

Abstract

As the central node between nutrition signaling input and the metabolic pathway, AMP-activated protein kinase (AMPK) is tightly regulated to maintain energy homeostasis. Subcellular compartmentalization of AMPK is one of the critical regulations that enables AMPK to access proper targets and generate appropriate responses to specific perturbations and different levels of stress. One of the characterized localization mechanisms is RanGTPase-driven CRM1 that recognizes the nuclear export sequence (NES) on the α subunit to translocate AMPK into the cytoplasm. Nuclear localization putatively employs RanGTPase-driven importin that might recognize the nuclear localization signal (NLS) present on the AMPKα2 kinase domain. Nucleo-cytoplasmic shuttling of AMPK is influenced by multiple factors, such as starvation, exercise, heat shock, oxidant, cell density, and circadian rhythm. Tissue-specific localization, which distributes AMPK trimers with different combinations, has also been shown to be vital in maintaining tissue-specific metabolism. Tissue-specific and subcellular distribution of AMPK might be attributed to differences in the expression of the subunit, the stabilization by protein regulators, tissue activity, and the localization of AMPK activators. Considering the importance of AMPK localization in coordinating signaling and metabolism, further research is due to fully elucidate the largely unknown complex mechanism underlying this regulation.

Rapid metabolic reprogramming mediated by the AMP-activated protein kinase during the lytic cycle of Toxoplasma gondii

“…Once internalized in host cells, phosphorylation of AMPKα is reduced and a balance between energy producing catabolism and biomass synthesizing anabolism is achieved, enabling robust proliferation of the parasites. eukaryotes, AMPK shuttles between the nucleus and cytoplasm in a Ran GTPase-dependent manner and such shuttling can be modulated by stresses 41 . Our results showed that phosphorylation and activation of Toxoplasma AMPK was drastically increased upon the release of intracellular parasites into extracellular environments.…”

Exposure to elevated temperature affects the expression of PIWI‐interacting RNAs and associated transcripts in mouse testes

“…29 It could be activated by many factors, like oxidant, circadian rhythm, heat shock, starvation, and hypoxia. 30 Several studies revealed that AMPK could promote the initiation of autophagy via activating Ulk1 through phosphorylating Ulk1 Ser317 and Ser777. 31,32 Besides, AMPK could directly phospho-rylate Beclin-1, which is the component of Ulk1 downstream complex during the process of autophagosome formation.…”

“…The AMPK is a highly conserved αβγ heterotrimeric serine‐threonine kinase that could regulate cellular energy homeostasis via sensing the concentrations of AMP 29 . It could be activated by many factors, like oxidant, circadian rhythm, heat shock, starvation, and hypoxia 30 . Several studies revealed that AMPK could promote the initiation of autophagy via activating Ulk1 through phosphorylating Ulk1 Ser317 and Ser777 31,32 .…”

Metabolic shift and the effect of mitochondrial respiration on the osteogenic differentiation of dental pulp stem cells

“…Once activated, AMPK induces catabolic pathways to produce energy and prevents anabolic pathways, such as lipid and protein synthesis, to save energy ( Wanet et al, 2015 ). On the other hand, considerable evidence shows that AMPK regulates cell fate, including controlling stem cell pluripotency and differentiation ( Afinanisa, Cho & Seong, 2021 ; Fernandez-Veledo et al., 2013 ; Liu et al, 2021 ). In this study, CCCP-treated hDPSCs exhibited an elevated level of p-AMPK, showing that the energy sensor AMPK was involved in the process of metabolism that influenced differentiation.…”