RT Journal Article
SR Electronic
T1 Mitochondrial Aurora kinase A induces mitophagy by interacting with MAP1LC3 and Prohibitin 2
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000806
DO 10.26508/lsa.202000806
VO 4
IS 6
A1 Giulia Bertolin
A1 Marie-Clotilde Alves-Guerra
A1 Angélique Cheron
A1 Agnès Burel
A1 Claude Prigent
A1 Roland Le Borgne
A1 Marc Tramier
YR 2021
UL https://www.life-science-alliance.org/content/4/6/e202000806.abstract
AB Epithelial and haematologic tumours often show the overexpression of the serine/threonine kinase AURKA. Recently, AURKA was shown to localise at mitochondria, where it regulates mitochondrial dynamics and ATP production. Here we define the molecular mechanisms of AURKA in regulating mitochondrial turnover by mitophagy. AURKA triggers the degradation of Inner Mitochondrial Membrane/matrix proteins by interacting with core components of the autophagy pathway. On the inner mitochondrial membrane, the kinase forms a tripartite complex with MAP1LC3 and the mitophagy receptor PHB2, which triggers mitophagy in a PARK2/Parkin–independent manner. The formation of the tripartite complex is induced by the phosphorylation of PHB2 on Ser39, which is required for MAP1LC3 to interact with PHB2. Last, treatment with the PHB2 ligand xanthohumol blocks AURKA-induced mitophagy by destabilising the tripartite complex and restores normal ATP production levels. Altogether, these data provide evidence for a role of AURKA in promoting mitophagy through the interaction with PHB2 and MAP1LC3. This work paves the way to the use of function-specific pharmacological inhibitors to counteract the effects of the overexpression of AURKA in cancer.