title: Mitochondrial delivery of bongkrekic acid using a MITO-Porter prevents the induction of apoptosis in human HeLa cells.
abstract: The fact that mitochondrial dysfunction has been implicated in a variety of human diseases suggests that they would be expected as a target organelle for these diseases. Bongkrekic acid (BKA) is a chemical that functions as a ligand of the adenine nucleotide translocator and is known to potently inhibit the mitochondrial permeability transition that is associated with apoptosis. Thus, delivering it to mitochondria would be an innovative therapy for the treatment of mitochondrial diseases that are largely associated with apoptosis. Here, we report on the use of a MITO-Porter, an innovative nanocarrier for mitochondrial delivery via mitochondrial membrane fusion, for delivering BKA to mitochondria. We first constructed a BKA-MITO-Porter, in which BKA is contained in lipid envelopes of a MITO-Porter. We then confirmed that the BKA-MITO-Porter was efficiently internalized into cells and is delivered to mitochondria, similar to a conventional MITO-Porter. Moreover, we evaluated the antiapoptosis effect of the BKA-MITO-Porter in HeLa cells by measuring caspase 3/7 activity. The findings confirmed that the BKA-MITO-Porter showed a strong antiapoptosis effect compared with naked BKA. The results reported here demonstrate its potential for the use in therapies aimed at mitochondrial diseases, as a mitochondrial medicine candidate.
authors: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan.
authors: Yuma
authors: Y
authors: Yamada
authors: Kohei
authors: K
authors: Nakamura
authors: Ryo
authors: R
authors: Furukawa
authors: Eriko
authors: E
authors: Kawamura
authors: Takuya
authors: T
authors: Moriwaki
authors: Kenji
authors: K
authors: Matsumoto
authors: Katsuhiro
authors: K
authors: Okuda
authors: Mitsuru
authors: M
authors: Shindo
authors: Hideyoshi
authors: H
authors: Harashima
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001865:Bongkrekic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D008081:Liposomes; D001865:Bongkrekic Acid