title: The non-canonical Wnt/PKC pathway regulates mitochondrial dynamics through degradation of the arm-like domain-containing protein Alex3.
abstract: The regulation of mitochondrial dynamics is vital in complex cell types, such as neurons, that transport and localize mitochondria in high energy-demanding cell domains. The Armcx3 gene encodes a mitochondrial-targeted protein (Alex3) that contains several arm-like domains. In a previous study we showed that Alex3 protein regulates mitochondrial aggregation and trafficking. Here we studied the contribution of Wnt proteins to the mitochondrial aggregation and dynamics regulated by Alex3. Overexpression of Alex3 in HEK293 cells caused a marked aggregation of mitochondria, which was attenuated by treatment with several Wnts. We also found that this decrease was caused by Alex3 degradation induced by Wnts. While the Wnt canonical pathway did not alter the pattern of mitochondrial aggregation induced by Alex3, we observed that the Wnt/PKC non-canonical pathway regulated both mitochondrial aggregation and Alex3 protein levels, thereby rendering a mitochondrial phenotype and distribution similar to control patterns. Our data suggest that the Wnt pathway regulates mitochondrial distribution and dynamics through Alex3 protein degradation.
authors.affiliation: Department of Cell Biology, University of Barcelona, Barcelona, Spain.
authors.forename: Román
authors.initials: R
authors.lastname: Serrat
authors.forename: Guillermo
authors.initials: G
authors.lastname: López-Doménech
authors.forename: Serena
authors.initials: S
authors.lastname: Mirra
authors.forename: Martí
authors.initials: M
authors.lastname: Quevedo
authors.forename: Jordi
authors.initials: J
authors.lastname: Garcia-Fernàndez
authors.forename: Fausto
authors.initials: F
authors.lastname: Ulloa
authors.forename: Ferrán
authors.initials: F
authors.lastname: Burgaya
authors.forename: Eduardo
authors.initials: E
authors.lastname: Soriano
mesh_terms: D020816:Amino Acid Motifs; D051186:Armadillo Domain Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D063154:Mitochondrial Dynamics / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009281:Naphthalenes / Q000494:pharmacology; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D051186:Armadillo Domain Proteins; C585811:ARMCX3 protein, human; D024101:Mitochondrial Proteins; D009281:Naphthalenes; D047428:Protein Kinase Inhibitors; D051153:Wnt Proteins; D049452:Green Fluorescent Proteins; D011493:Protein Kinase C; C058819:calphostin C