LKB1/AMPK Pathway and Drug Response in Cancer: A Therapeutic Perspective
Table 1
Mitochondrial dynamics control by LKB1-AMPK.
Target
Role of LKB1
Biological effects
(a) Role of LKB1/AMPK in mitochondrial fission
MFF (mitochondrial fission factor)
AMPK-mediated phosphorylation
MFF phosphorylation relocalizes the cytosolic GTPase Dynamin-Related Protein 1 (DRP1) to mitochondria, leading to mitochondrial fragmentation [138]
ULK1 (Unc-51-Like Autophagy Activating Kinase 1)
AMPK-mediated phosphorylation
ULK1 phosphorylation initiates mitophagy of damaged mitochondria, providing cancer cells with an important loophole from therapy-induced cytotoxicity [139]
Activation of PGC-1α, the master regulator of mitochondrial biogenesis, promotes the biogenesis of new mitochondria, in order to preserve mitochondrial network functionality [139]
(b) Role of LKB1/AMPK in mitochondrial fusion
MFN1 (Mitofusin-1)
AMPK-mediated upregulation
MFN1 mediates outer mitochondrial membrane fusion, protecting cells from mitochondrial dysfunction following a cytotoxic injury [140]
OPA1 (Optic Atrophy 1)
AMPK-mediated upregulation
OPA1 mediates inner mitochondrial membrane fusion, protecting cells from mitochondrial dysfunction following a cytotoxic injury [140]