title: AMPK maintains energy homeostasis and survival in cancer cells via regulating p38/PGC-1α-mediated mitochondrial biogenesis.
abstract: Cancer cells exhibit unique metabolic response and adaptation to the fluctuating microenvironment, yet molecular and biochemical events imprinting this phenomenon are unclear. Here, we show that metabolic homeostasis and adaptation to metabolic stress in cancer cells are primarily achieved by an integrated response exerted by the activation of AMPK. We provide evidence that AMPK-p38-PGC-1α axis, by regulating energy homeostasis, maintains survival in cancer cells under glucose-limiting conditions. Functioning as a molecular switch, AMPK promotes glycolysis by activating PFK2, and facilitates mitochondrial metabolism of non-glucose carbon sources thereby maintaining cellular ATP level. Interestingly, we noted that AMPK can promote oxidative metabolism via increasing mitochondrial biogenesis and OXPHOS capacity via regulating expression of PGC-1α through p38MAPK activation. Taken together, our study signifies the fundamental role of AMPK in controlling cellular bioenergetics and mitochondrial biogenesis in cancer cells.
authors.affiliation: National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind , Pune, Maharashtra 411 007, India.
authors.forename: B
authors.initials: B
authors.lastname: Chaube
authors.affiliation: National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind , Pune, Maharashtra 411 007, India.
authors.forename: P
authors.initials: P
authors.lastname: Malvi
authors.affiliation: National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind , Pune, Maharashtra 411 007, India.
authors.forename: S V
authors.initials: SV
authors.lastname: Singh
authors.affiliation: National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind , Pune, Maharashtra 411 007, India.
authors.forename: N
authors.initials: N
authors.lastname: Mohammad
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Viollet
authors.affiliation: National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind , Pune, Maharashtra 411 007, India.
authors.forename: M K
authors.initials: MK
authors.lastname: Bhat