title: Long-term inhibition of cyclophilin D results in intracellular translocation of calcein AM from mitochondria to lysosomes.
abstract: Cyclophilin D is a peptidyl-prolyl cis-trans isomerase localized in the mitochondrial matrix. Although its effects on mitochondrial characteristics have been well studied, its relation to the uptake of molecules by mitochondria remains unknown. Here, we demonstrated the effects of cyclophilin D on the intracellular translocation of calcein AM. Following addition of calcein AM to control cells or cells overexpressing wild-type cyclophilin D, calcein fluorescence was observed in mitochondria. However, long-term inhibition of cyclophilin D in these cells altered the localization of calcein fluorescence from mitochondria to lysosomes without changing mitochondrial esterase activity. In addition, depletion of glucose from the medium recovered calcein localization from lysosomes to mitochondria. This is the first demonstration of the effects of cyclophilin D on the intracellular translocation of molecules other than proteins and suggests that cyclophilin D may modify mitochondrial features by inducing the translocation of molecules to the mitochondria through the mechanism associated with cellular energy metabolism.
authors.affiliation: Division of Biotechnology and Life Sciences, Institute of Engineering, Tokyo University of Agriculture and Technology, Nakacho 2-24-16, Koganei, Tokyo 184-8588, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shinohe
authors.affiliation: Division of Biotechnology and Life Sciences, Institute of Engineering, Tokyo University of Agriculture and Technology, Nakacho 2-24-16, Koganei, Tokyo 184-8588, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Kobayashi
authors.affiliation: Division of Biotechnology and Life Sciences, Institute of Engineering, Tokyo University of Agriculture and Technology, Nakacho 2-24-16, Koganei, Tokyo 184-8588, Japan.
authors.forename: Marina
authors.initials: M
authors.lastname: Gotoh
authors.affiliation: Division of Biotechnology and Life Sciences, Institute of Engineering, Tokyo University of Agriculture and Technology, Nakacho 2-24-16, Koganei, Tokyo 184-8588, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Division of Biotechnology and Life Sciences, Institute of Engineering, Tokyo University of Agriculture and Technology, Nakacho 2-24-16, Koganei, Tokyo 184-8588, Japan. Electronic address: ohta@cc.tuat.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ohta
mesh_terms: D000818:Animals; D002460:Cell Line; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005452:Fluoresceins / Q000737:chemistry*; D005947:Glucose / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D019745:cis-trans-Isomerases / Q000378:metabolism; D000097322:Peptidyl-Prolyl Isomerase D
chemical_list: D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins; D005452:Fluoresceins; D005947:Glucose; D033681:Mitochondrial Membrane Transport Proteins; D019745:cis-trans-Isomerases; C085925:calcein AM; C114456:PPID protein, human; D000097322:Peptidyl-Prolyl Isomerase D; C007740:fluorexon
keywords: Calcein AM; Cyclophilin D; Lysosomes; Mitochondria