title: Characteristics of Mitochondrial Transformation into Human Cells.
abstract: Mitochondria can be incorporated into mammalian cells by simple co-incubation of isolated mitochondria with cells, without the need of transfection reagents or any other type of intervention. This phenomenon was termed mitochondrial transformation, and although it was discovered in 1982, currently little is known regarding its mechanism(s). Here we demonstrate that mitochondria can be transformed into recipient cells very quickly, and co-localize with endogenous mitochondria. The isolated mitochondria interact directly with cells, which engulf the mitochondria with cellular extensions in a way, which may suggest the involvement of macropinocytosis or macropinocytosis-like mechanisms in mitochondrial transformation. Indeed, macropinocytosis inhibitors but not clathrin-mediated endocytosis inhibition-treatments, blocks mitochondria transformation. The integrity of the mitochondrial outer membrane and its proteins is essential for the transformation of the mitochondria into cells; cells can distinguish mitochondria from similar particles and transform only intact mitochondria. Mitochondrial transformation is blocked in the presence of the heparan sulfate molecules pentosan polysulfate and heparin, which indicate crucial involvement of cellular heparan sulfate proteoglycans in the mitochondrial transformation process.
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada (IMRIC), Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, 91120, Israel.
authors.forename: E E
authors.initials: EE
authors.lastname: Kesner
authors.affiliation: Monique and Jacques Roboh Department of Genetic Research, Department of Genetics and Metabolic Diseases, Hadassah, Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Saada-Reich
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada (IMRIC), Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, 91120, Israel.
authors.forename: H
authors.initials: H
authors.lastname: Lorberboum-Galski
mesh_terms: D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D010873:Pinocytosis
chemical_list: D019812:Heparan Sulfate Proteoglycans