FUNDC1-mediated mitophagy in bovine papillomavirus-infected urothelial cells

Publication date: Available online 24 May 2019Source: Veterinary MicrobiologyAuthor(s): Sante Roperto, Valeria Russo, Francesca De Falco, Alessandra Rosati, Cornel Catoi, Franco RopertoAbstractE5 protein, the major oncoprotein of the bovine Deltapapillomavirus genus, has been detected in 17 of the 19 urothelial cancers by molecular and morphological procedures. In 10 urothelial cancers, the oxygen sensitive subunit HIF-1α, which is upregulated by hypoxia, was overexpressed. Mitophagy, the selective autophagic removal of dysfunctional mitochondria, was upregulated in hypoxic neoplastic cells infected by BPVs which was mediated by FUNDC1, a mitochondrial outer-membrane protein. The FUNDC1 receptor was amplified by PCR, and amplicon sequencing showed a 100% homology with bovine FUNDC1 sequences deposited in GenBank (accession number: NM_001104982). Both transcripts and protein levels of FUNDC1 were significantly decreased in hypoxic neoplastic cells relative to healthy, non-neoplastic cells. FUNDC1 interacted with the LC3 protein, a marker of autophagosome (mitophagosome) membrane, the Hsc70/Hsp70 chaperone, and Bag3 co-chaperone. Bag3 may play a role in mitophagosome formation together with the Synpo2 protein, and may be involved in the degradation of Hsc70/Hsp70-bound CHIP-ubiquitinated cargoes, in association with its chaperone. Ultrastructural findings revealed the presence of mitochondria exhibiting severe fragmentation and loss of cristae, as well as numerous mitochondria...
Source: Veterinary Microbiology - Category: Veterinary Research Source Type: research