title: Chondrocyte protein with a poly-proline region (CHPPR) is a novel mitochondrial protein and promotes mitochondrial fission.
abstract: We have recently identified a chondrocyte protein with a poly-proline region, referred to as CHPPR, and showed that this protein is expressed intracellularly in chick embryo chondrocytes. Conventional fluorescence and confocal localization of CHPPR shows that CHPPR is sorted to mitochondria. Furthermore, immunoelectron microscopy of CHPPR transfected cells demonstrates that this protein is mostly associated with the mitochondrial inner membranes. Careful analysis of CHPPR expressing cells reveals, instead of the regular mitochondrial tubular network, the presence of a number of small spheroid mitochondria. Here we show that the domain responsible for network-spheroid transition spans amino acid residues 182-309 including the poly-proline region. Functional analyses of mitochondrial activity rule out the possibility of mitochondrial damage in CHPPR transfected cells. Since cartilage expresses high levels of CHPPR mRNA when compared to other tissues and because CHPPR is associated with late stages of chondrocyte differentiation, we have investigated mitochondrial morphology in hypertrophic chondrocytes by MitoTracker Orange labeling. Confocal microscopy shows that these cells have spheroid mitochondria. Our data demonstrate that CHPPR is able to promote mitochondrial fission with a sequence specific mechanism suggesting that this event may be relevant to late stage of chondrocyte differentiation.
authors.affiliation: Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Tonachini
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Monticone
authors.forename: Claudia
authors.initials: C
authors.lastname: Puri
authors.forename: Carlo
authors.initials: C
authors.lastname: Tacchetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Pinton
authors.forename: Rosario
authors.initials: R
authors.lastname: Rizzuto
authors.forename: Ranieri
authors.initials: R
authors.lastname: Cancedda
authors.forename: Sara
authors.initials: S
authors.lastname: Tavella
authors.forename: Patrizio
authors.initials: P
authors.lastname: Castagnola
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002645:Chickens; D002522:Chlorocebus aethiops; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D003198:Computer Simulation; D006801:Humans; D006984:Hypertrophy; D051379:Mice; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010455:Peptides / Q000378:metabolism*; D021381:Protein Transport; D018892:Proton-Motive Force; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: C493867:CHPPR protein, mouse; D024101:Mitochondrial Proteins; D010455:Peptides; D012333:RNA, Messenger; C011083:polyproline; D002118:Calcium