Review
Biotechnology & Applied Microbiology
Yuma Yamada, Sen Ishizuka, Manae Arai, Minako Maruyama, Hideyoshi Harashima
Summary: This review summarizes the current state of research on RNA-based therapeutics targeted to mitochondria, emphasizing on mitochondrial RNA delivery therapies and therapies involving the use of mitochondrial genome editing devices. Methods for delivering nucleic acids to mitochondria are needed in order to realize such innovative therapies.
EXPERT OPINION ON BIOLOGICAL THERAPY
(2022)
Review
Chemistry, Multidisciplinary
Xiaolu Guo, Naidi Yang, Wenhui Ji, Hang Zhang, Xiao Dong, Zhiqiang Zhou, Lin Li, Han-Ming Shen, Shao Q. Yao, Wei Huang
Summary: Traditional cancer therapies such as surgery, chemotherapy, and radiotherapy have limited effectiveness, while photodynamic therapy, photothermal therapy, and chemodynamic therapy have shown promising results in cancer treatment due to their high selectivity, minimal resistance, and minimal toxicity.
ADVANCED MATERIALS
(2021)
Review
Pharmacology & Pharmacy
Ruben Faria, Prisca Boisguerin, Angela Sousa, Diana Costa
Summary: Mitochondria are crucial cellular organelles responsible for energy production in cells, and mutations in their DNA (mtDNA) can lead to various diseases. Mitochondrial gene therapy is a promising strategy to address these disorders. Developing efficient mtDNA-based delivery systems to target and transfect mammalian mitochondria is an exciting area of research that can contribute to restoring normal mitochondrial function.
Review
Biochemistry & Molecular Biology
Simone Patergnani, Esmaa Bouhamida, Sara Leo, Paolo Pinton, Alessandro Rimessi
Summary: The decline in mitochondrial redox homeostasis is associated with the development of inflammatory-related diseases, with mitochondria playing a key role in triggering inflammation and enhancing the inflammatory response. Evidence supports the concept of mito-inflammation, where mitochondrial-derived reactive oxygen species exacerbate inflammation in various diseases.
Article
Chemistry, Medicinal
Yuma Yamada, Takuya Ishimaru, Kohei Ikeda, Hideyoshi Harashima
Summary: This study demonstrates the delivery of vitamin B1 to mitochondria to enhance ATP production through activating the TCA cycle; MITO-Porter containing encapsulated vitamin B1 efficiently accumulated in mitochondria of neuroblast model cells; ATP production significantly increased after MITO-Porter (VB1) treatment compared to naked vitamin B1.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yusuke Kimura, Hironori Saito, Tatsuya Osaki, Yasuhiro Ikegami, Taisei Wakigawa, Yoshiho Ikeuchi, Shintaro Iwasaki
Summary: Mitochondria have their own genome that encodes components of oxidative phosphorylation complexes, and mitochondrial ribosomes translate the mRNAs expressed from the mitochondrial genome. Cellular heterogeneity in mitochondrial translation can be expected due to the differential OXPHOS activity observed in different cell types and growth conditions. In this study, researchers developed a technique called mito-FUNCAT-FACS that allows the labeling and sorting of newly synthesized mitochondrial proteins using a click chemistry-compatible methionine analog. This approach provides a useful tool for examining mitochondrial protein synthesis in individual cells.
Article
Biochemistry & Molecular Biology
Jae-Sung Kim, Ye-Ram Kim, Sein Jang, Sang Geon Wang, Euni Cho, Seok-Jun Mun, Hye-In Jeon, Hyo-Keun Kim, Sun-Joon Min, Chul-Su Yang
Summary: Rubicon interacts with p22phox to regulate ROS production in immune cells. Mito-TIPTP inhibits the interaction between Rubicon and p22phox, enhancing mitochondrial function and showing therapeutic effects in colitis models. This suggests Mito-TIPTP as a potential therapeutic agent for colitis by targeting the Rubicon-p22phox interaction.
Review
Biochemistry & Molecular Biology
Javier Ramon, Ferran Vila-Julia, David Molina-Granada, Miguel Molina-Berenguer, Maria Jesus Melia, Elena Garcia-Arumi, Javier Torres-Torronteras, Yolanda Camara, Ramon Marti
Summary: MDDS is a group of mitochondrial diseases caused by dysfunctional mtDNA replication, and current treatment options are limited. Advances in understanding the biochemical pathomechanisms have led to new strategies ranging from small molecule enhancement to gene therapy for the treatment of these diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Medicine, Research & Experimental
Timofei Chernega, Jaehyoung Choi, Leonardo Salmena, Ana Cristina Andreazza
Summary: This article investigates the current treatment options for mitochondrial diseases and explores the potential of RNA-based therapeutic strategies, including the use of ASOs and RNAi drugs, allotopic therapies, and RNA-based antigenomic therapies. Furthermore, various mechanisms for delivering RNA therapeutic agents to the mitochondrial matrix are reviewed.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Review
Ophthalmology
Marco H. Ji, Alexander Kreymerman, Kinsley Belle, Benjamin K. Ghiam, Stephanie P. Muscat, Vinit B. Mahajan, Gregory M. Enns, Mark Mercola, Edward H. Wood
Summary: Mitochondrial dysfunction plays a significant role in various eye diseases, affecting both rare conditions like LHON and common diseases such as glaucoma and diabetic retinopathy. Therapies targeting mitochondrial function have shown promise, with approved treatments like photobiomodulation for AMD and idebenone for LHON, as well as promising results from trials with Elamipretide and GS010 gene therapy. Mitochondria are recognized as viable therapeutic targets for a broad range of ocular diseases.
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
(2021)
Article
Microbiology
Takeshi Ito, Sayaka Kajita, Minori Fujii, Yasuo Shinohara
Summary: Malate-quinone oxidoreductase (MQO), a Plasmodium membrane protein, plays an important role in the tricarboxylic acid (TCA) cycle and the electron transport chain (ETC). Through a yeast expression system, it has been demonstrated that MQO can complement the metabolic function of yeast mitochondrial malate dehydrogenase. This study is important for understanding the metabolism of Plasmodium parasites and developing novel antimalarial drugs.
MICROBIOLOGY SPECTRUM
(2023)
Article
Immunology
Prasad Kisan Tambe, H. S. Qsee, Sanjay Bharati
Summary: This study investigated the protective effect of Mito-TEMPO against 5-FU-induced intestinal toxicity. The results showed that Mito-TEMPO pre-treatment improved intestinal histopathological alterations, reduced inflammatory cell infiltration and apoptotic cell death, and improved mitochondrial function and oxidative stress. Therefore, Mito-TEMPO may be used as an adjuvant therapy in 5-FU chemotherapy.
INFLAMMOPHARMACOLOGY
(2023)
Article
Biology
Guillermo Carbajosa, Aminah T. Ali, Alan Hodgkinson
Summary: This study develops a method to detect and quantify mitochondrial RNA cleavage events and applies it to human whole blood data. It identifies novel cleavage junctions associated with mitochondrial RNA processing, implicates multiple genes in modulating mitochondrial RNA cleavage, and detects the potential impact of variation in cleavage rates on downstream phenotypes and disease processes.
Review
Biochemistry & Molecular Biology
Xingbo Yang, Jiacheng Jiang, Zongyu Li, Jiayi Liang, Yaozu Xiang
Summary: Mitochondria, as the energy powerhouse of cells, have their own unique genome separate from the nuclear genome. Mutations in mitochondrial DNA can lead to diseases and health issues, but editing these genes effectively remains a challenge. Current gene editing technologies have been explored for mitochondrial gene editing, but further research and optimization are needed for their application in this specific area.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Review
Pharmacology & Pharmacy
Alessia Di Donfrancesco, Giulia Massaro, Ivano Di Meo, Valeria Tiranti, Emanuela Bottani, Dario Brunetti
Summary: This article provides a comprehensive overview of the application of gene therapy in mitochondrial diseases (MDs), addressing the main challenges, feasible solutions, and future prospects.
Review
Biochemistry & Molecular Biology
Yuma Yamada, Yuta Takano, Satrialdi, Jiro Abe, Mitsue Hibino, Hideyoshi Harashima
Letter
Clinical Neurology
Nurun Nahar Borna, Yoshihito Kishita, Jiro Abe, Takuro Furukawa, Minako Ogawa-Tominaga, Takuya Fushimi, Atsuko Imai-Okazaki, Atsuhito Takeda, Akira Ohtake, Kei Murayama, Yasushi Okazaki
Article
Chemistry, Medicinal
Yuma Yamada, Reina Munechika, Satrialdi, Fumika Kubota, Yusuke Sato, Yu Sakurai, Hideyoshi Harashima
JOURNAL OF PHARMACEUTICAL SCIENCES
(2020)
Article
Cell Biology
Yuma Yamada, Yutaka Fukuda, Daisuke Sasaki, Minako Maruyama, Hideyoshi Harashima
Article
Multidisciplinary Sciences
Yuma Yamada, Kana Somiya, Akihiko Miyauchi, Hitoshi Osaka, Hideyoshi Harashima
SCIENTIFIC REPORTS
(2020)
Article
Pathology
Atsuhito Takeda, Kei Murayama, Yasushi Okazaki, Atsuko Imai-Okazaki, Akira Ohtake, Emi Takakuwa, Hirokuni Yamazawa, Gaku Izumi, Jiro Abe, Ayako Nagai, Kota Taniguchi, Daisuke Sasaki, Takao Tsujioka, John M. Basgen
Summary: The study aimed to add myocardial pathology to the diagnostic criteria for mitochondrial respiratory chain disorders in patients with mitochondrial cardiomyopathy (MCM). Results showed that a pathological diagnosis of MCM could be confirmed by a quantitative study of electron microscopy and immunohistopathological analysis using the mitochondrial respiratory chain enzyme subunit antibody. Four patients were diagnosed with MCM based on the recent criteria of mitochondrial respiratory chain disorders.
JOURNAL OF CLINICAL PATHOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Yusuke Sato, Takashi Nakamura, Yuma Yamada, Hideyoshi Harashima
Summary: The era of nanomedicine has arrived, with lipid nanoparticle (LNP) technology successfully delivering siRNA to treat genetic diseases and COVID-19 mRNA vaccines. New lipids for LNP formulations and mechanisms of targeting without ligands are discussed. Clinical applications of nano DDS in cancer immunology and new cancer therapy targeting mitochondria are also highlighted.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Chemistry, Medicinal
Yuma Yamada, Takuya Ishimaru, Kohei Ikeda, Hideyoshi Harashima
Summary: This study demonstrates the delivery of vitamin B1 to mitochondria to enhance ATP production through activating the TCA cycle; MITO-Porter containing encapsulated vitamin B1 efficiently accumulated in mitochondria of neuroblast model cells; ATP production significantly increased after MITO-Porter (VB1) treatment compared to naked vitamin B1.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Takao Tsujioka, Daisuke Sasaki, Atsuhito Takeda, Hideyoshi Harashima, Yuma Yamada
Summary: The therapeutic potential of a myocardial mitochondria-targeting liposome encapsulating the cardioprotective compound resveratrol was evaluated in this study. The liposome was readily taken up by myocardial cells and localized to intracellular mitochondria. It significantly activated cellular mitochondrial function without causing cellular toxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Jiro Abe, Mamoru Honda, Daisuke Sasaki, Kota Taniguchi, Gaku Izumi, Takuo Furukawa, Hirokuni Yamazawa, Kohta Takei, Atsuhito Takeda
Summary: This study validated the limitations of the AL method in estimating left ventricular volume, particularly in patients with Tetralogy of Fallot (TOF). The study compared angiographic data of TOF patients with a control group, revealing a significant difference in the long axis lengths between AP and LT views. This discrepancy resulted in an overestimation of LVEDV in the TOF group. Cardiac MRI analyses further supported this finding.
Article
Multidisciplinary Sciences
Daisuke Sasaki, Jiro Abe, Atsuhito Takeda, Hideyoshi Harashima, Yuma Yamada
Summary: This study aimed to validate the therapeutic effect of cell transplantation by using mitochondria-activated stem cells (MITO cells) in a mouse model of myocardial ischemia-reperfusion. The results showed that MITO cells transplanted group had better therapeutic effects, including weight gain, cardiac function improvement, and inhibition of fibrosis, compared to the non-transplanted group and CPC group.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Takafumi Fukui, Hironao Tateno, Takashi Nakamura, Yuma Yamada, Yusuke Sato, Norimasa Iwasaki, Hideyoshi Harashima, Ken Kadoya
Summary: This study investigated the potential of liposomes as an efficient drug-delivery system for treating disorders of the central nervous system. By optimizing the liposomes and conducting experiments in a rat model, the study confirmed successful retrograde transport to the spinal cord and dorsal root ganglia. Modifying the liposomes with different substances improved their transport efficiency, providing valuable insights for the future development of novel DDS targeting the CNS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Ikuma Hori, Hideyoshi Harashima, Yuma Yamada
Summary: Delivering drugs to mitochondria, the main source of energy in neurons, is a potential therapeutic strategy for neurodegenerative diseases. This paper focuses on the efficient delivery of the drug berberine (BBR) into mitochondria using a lipid nanoparticle and its pharmacological action in Neuro2a cells, showing increased ATP production and expression of mitochondrial ubiquitin ligase (MITOL). The findings highlight the importance of enhancing the accumulation of BBR in mitochondria for improved therapeutic effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yuma Yamada, Shinnosuke Daikuhara, Atsushi Tamura, Kei Nishida, Nobuhiko Yui, Hideyoshi Harashima
Summary: Activation of autophagy by Me-PRX and MITO-Porter (Me-PRX) in different intracellular organelles plays an important role in autophagy induction. The level of autophagy induction and organelle injury vary depending on the route of administration. These findings highlight the significance of targeting specific organelles for efficient autophagy induction.