title: BECN1 is involved in the initiation of mitophagy: it facilitates PARK2 translocation to mitochondria.
abstract: The autophagy protein BECN1/Beclin 1 is known to play a central role in autophagosome formation and maturation. The results presented here demonstrate that BECN1 interacts with the Parkinson disease-related protein PARK2. This interaction does not require PARK2 translocation to mitochondria and occurs mostly in cytosol. However, our results suggest that BECN1 is involved in PARK2 translocation to mitochondria because loss of BECN1 inhibits CCCP- or PINK1 overexpression-induced PARK2 translocation. Our results also demonstrate that the observed PARK2-BECN1 interaction is functionally important. Measurements of the level of MFN2 (mitofusin 2), a PARK2 substrate, demonstrate that depletion of BECN1 prevents PARK2 translocation-induced MFN2 ubiquitination and loss. BECN1 depletion also rescues the MFN2 loss-induced suppression of mitochondrial fusion. In sum, our results demonstrate that BECN1 interacts with PARK2 and regulates PARK2 translocation to mitochondria as well as PARK2-induced mitophagy prior to autophagosome formation.
authors.affiliation: Department of Pharmacology; Centre of Excellence for Translational Medicine; University of Tartu; Tartu, Estonia.
authors.forename: Vinay
authors.initials: V
authors.lastname: Choubey
authors.affiliation: Department of Pharmacology; Centre of Excellence for Translational Medicine; University of Tartu; Tartu, Estonia.
authors.forename: Michal
authors.initials: M
authors.lastname: Cagalinec
authors.affiliation: Department of Pharmacology; Centre of Excellence for Translational Medicine; University of Tartu; Tartu, Estonia.
authors.forename: Joanna
authors.initials: J
authors.lastname: Liiv
authors.affiliation: Department of Pharmacology; Centre of Excellence for Translational Medicine; University of Tartu; Tartu, Estonia.
authors.forename: Dzhamilja
authors.initials: D
authors.lastname: Safiulina
authors.affiliation: Department of Pharmacology; Centre of Excellence for Translational Medicine; University of Tartu; Tartu, Estonia.
authors.forename: Miriam A
authors.initials: MA
authors.lastname: Hickey
authors.affiliation: Department of Pharmacology; Centre of Excellence for Translational Medicine; University of Tartu; Tartu, Estonia.
authors.forename: Malle
authors.initials: M
authors.lastname: Kuum
authors.affiliation: Department of Pharmacology; Centre of Excellence for Translational Medicine; University of Tartu; Tartu, Estonia.
authors.forename: Mailis
authors.initials: M
authors.lastname: Liiv
authors.affiliation: Department of Biosciences; Division of Biochemistry and Biotechnology; University of Helsinki; Helsinki, Finland.
authors.forename: Tahira
authors.initials: T
authors.lastname: Anwar
authors.affiliation: Department of Biosciences; Division of Biochemistry and Biotechnology; University of Helsinki; Helsinki, Finland.
authors.forename: Eeva-Liisa
authors.initials: EL
authors.lastname: Eskelinen
authors.affiliation: Department of Pharmacology; Centre of Excellence for Translational Medicine; University of Tartu; Tartu, Estonia.
authors.forename: Allen
authors.initials: A
authors.lastname: Kaasik
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1; D001693:Biological Transport, Active; D002478:Cells, Cultured; D020558:GTP Phosphohydrolases; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D063306:Mitophagy / Q000502:physiology*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D016716:PC12 Cells; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D000099202:PTEN-Induced Putative Kinase
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D020558:GTP Phosphohydrolases; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D050505:Mutant Proteins; D011494:Protein Kinases; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C512829:Becn1 protein, rat; C111567:parkin protein; C489710:Mfn2 protein, rat
keywords: BECN1; MFN2; PARK2 translocation; mitochondrial dynamics; mitophagy