Article
Clinical Neurology
Arianna Manini, Megi Meneri, Carmelo Rodolico, Stefania Corti, Antonio Toscano, Giacomo Pietro Comi, Olimpia Musumeci, Dario Ronchi
Summary: Biallelic TK2 mutations are linked to a spectrum of clinical presentations affecting skeletal muscle, with childhood-onset forms typically causing rapidly progressive muscle weakness and respiratory impairment. A case study of an Italian patient with slowly progressive mitochondrial myopathy expands the genetic background of TK2-related myopathy, demonstrating clinical overlap among different forms.
FRONTIERS IN NEUROLOGY
(2022)
Article
Multidisciplinary Sciences
F. X. Reymond Sutandy, Ines Goessner, Georg Tascher, Christian Muench
Summary: This study demonstrates that cytosol-mitochondrial reactive oxygen species (mtROS) and accumulation of mitochondrial protein precursors in the cytosol (c-mtProt) play a critical role in initiating the mitochondrial unfolded protein response (UPRmt). The findings reveal a link between mitochondrial and cytosolic proteostasis and provide molecular insight into UPRmt signaling in human cells.
Article
Biochemistry & Molecular Biology
Carolyn K. J. Young, Joel H. Wheeler, Md Mostafijur Rahman, Matthew J. Young
Summary: Nucleoside reverse transcriptase inhibitors may cause mitochondrial toxicity and affect mtDNA replication, with potential value for anticancer purposes. HepaRG cell line can be a useful model to study the toxic effects of NRTIs, observing changes in mtDNA levels and cellular bioenergetics parameters.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Mansoor Hussain, Xixia Chu, Burcin Duan Sahbaz, Samuel Gray, Komal Pekhale, Jae-Hyeon Park, Deborah L. Croteau, Vilhelm A. Bohr
Summary: Aging is associated with decreased DNA repair efficiency and increased inflammation, contributing to age-related diseases. Mitochondrial OGG1 plays a role in DNA repair and improved mitochondrial function. Overexpression of mitochondria-targeted OGG1 can reverse aging-associated inflammation and improve functions in mice. The release of mtDNA into the cytoplasm is regulated by mtOGG1, which controls age-associated inflammation.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Hua Guan, Wen Zhang, Dafei Xie, Yuehua Nie, Shi Chen, Xiaoya Sun, Hongling Zhao, Xiaochang Liu, Hua Wang, Xin Huang, Chenjun Bai, Bo Huang, Pingkun Zhou, Shanshan Gao
Summary: Mitochondria is a vital organelle affected by ionizing radiation (IR) outside the nucleus. This study investigates the impact and role of cytosolic mitochondrial DNA (mtDNA) and associated cGAS signaling on hematopoietic injury caused by IR in both in vitro and in vivo models. The findings reveal that IR exposure promotes the release of mtDNA into the cytosol, activating the cGAS signaling pathway. Furthermore, inhibiting VDAC1 and cGAS synthetase can mitigate bone marrow injury and ameliorate hematopoietic suppression induced by IR. This research provides insights into the non-target effects of radiation and offers a potential strategy for preventing and treating hematopoietic acute radiation syndrome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
David Molina-Granada, Emiliano Gonzalez-Vioque, Marris G. Dibley, Raquel Cabrera-Perez, Antoni Vallbona-Garcia, Javier Torres-Torronteras, Leonid A. Sazanov, Michael T. Ryan, Yolanda Camara, Ramon Marti
Summary: Imbalanced mitochondrial dNTP pools play a crucial role in the pathogenesis of various human diseases. This study reveals that dGTP is overrepresented among other dNTPs in mitochondria and is mainly bound to NDUFA10, an accessory subunit of complex I of the mitochondrial respiratory chain. Mutations in the dNK domain of NDUFA10 lead to reduced dGTP binding capacity and decrease mitochondrial dGTP content, suggesting a potential mechanism linking mitochondrial dNTP availability and oxidative metabolism.
COMMUNICATIONS BIOLOGY
(2022)
Article
Cell Biology
Daniela Bebbere, Susanne E. Ulbrich, Katrin Giller, Valeri Zakhartchenko, Horst-Dieter Reichenbach, Myriam Reichenbach, Paul J. Verma, Eckhard Wolf, Sergio Ledda, Stefan Hiendleder
Summary: The study reveals about 50% reduction in mitochondrial DNA (mtDNA) in the liver and skeletal muscle of SCNT fetuses at day 80 of gestation, with no significant decrease observed in the brain. The depletion of mtDNA is associated with hepatomegaly and muscle hypertrophy of SCNT fetuses, indicating that it is a major signature of perturbations after SCNT. The expression of selected nuclear-encoded genes pivotal for mtDNA replication is similar to controls, suggesting that the mitochondrial perturbation in interaction with incomplete nuclear reprogramming drives abnormal epigenetic features and correlated phenotypes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Naomoto Harada, Haruka Nagasaki, Hiromi Yamamoto, Kenji Matsubara, Takamasa Suzuki, Akira Gomori, Tatsushi Yokogawa, Kenichi Matsuo, Kazutaka Miyadera
Summary: Rodents have higher plasma thymidine levels compared to other mammals, including humans. A new knock-in mouse model with high expression of human thymidine phosphorylase was generated to study this difference in nucleotide metabolism. The knock-in mice exhibited growth retardation, decreased plasma thymidine levels, and various phenotypic abnormalities, which could be partially or completely rescued by the administration of a thymidine phosphorylase inhibitor. These findings suggest that the knock-in mouse model can be used to study mitochondrial diseases and investigate differences in nucleotide metabolism between humans and mice.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Cell Biology
Noa Kirschner Peretz, Sofia Segal, Ido Weiser-Bitoun, Yael Yaniv
Summary: In this study, FRET-based sensors were used to investigate the spatiotemporal cAMP/PKA signaling in different cellular compartments of atrial cells and its interaction with Ca2+. The results showed distinct PKA activity in different cellular compartments, regulated by Ca2+. This specific signaling pathway may play a role in the excitation and mitochondrial function of atrial cells.
Article
Urology & Nephrology
Nidhi Dwivedi, Abeda Jamadar, Sijo Mathew, Timothy A. Fields, Reena Rao
Summary: This study found that myofibroblasts in the kidneys of ADPKD patients can promote the proliferation of cyst epithelial cells, cyst growth, and fibrosis. Targeting this cell type could be a novel therapeutic strategy for treating ADPKD.
KIDNEY INTERNATIONAL
(2022)
Review
Cell Biology
Edmund Charles Jenkins, Mrittika Chattopadhyay, Doris Germain
Summary: Mitochondrial stress can induce cytosolic proteostasis, but the exact mechanisms are still unclear. The interaction between mitochondria and cytosolic proteostasis is crucial for treating proteopathies, and there is potential for stimulating mitochondrial-mediated cytosolic proteostasis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Jun Fan, Lili Deng, Ying Peng, Yuedi Ding
Summary: The study introduced an oncolytic virus delivery system to express somatostatin fusion protein, combining the anti-tumor effects of somatostatin and the oncolytic virus to destroy tumor tissues. The results showed that the vaccinia VG9/(SST-14)(2)-HSA recombinant possessed a combined anti-tumor effect and prolonged survival in mice. Vaccinia VG9/(SST-14)(2)-HSA is expected to become a potent therapeutic agent for cancer treatment.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Xiangfeng Niu, Ethan Stancliffe, Susan J. Gelman, Lingjue Wang, Michaela Schwaiger-Haber, Joe L. Rowles, Leah P. Shriver, Gary J. Patti
Summary: In this study, an approach to resolve the fluxes of NADPH in the cytosol and mitochondria was introduced using deuterium tracing. It was found that challenges in the cytosol affected NADPH fluxes in the cytosol, while challenges in the mitochondria affected NADPH fluxes in the mitochondria. This work highlights the value of using proline labeling as a reporter system for studying compartmentalized metabolism and reveals independent regulation of NADPH homeostasis in the cytosol and mitochondria, without evidence for NADPH shuttle activity.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Avery S. Ward, Chia-Heng Hsiung, Daniel G. Kesterson, Vasudeva G. Kamath, Edward E. McKee
Summary: The study demonstrates that ETV is a competitive inhibitor of dGK and dGK primarily plays a role in phosphorylation of dG.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Etienne E. Muller, Dumisile Maseko, Ranmini S. Kularatne
Summary: This study conducted phenotypic and genotypic surveillance on ACV resistance in HSV-2 derived from genital ulcer samples collected in a primary healthcare facility in South Africa. The results revealed no resistance-associated mutations, but identified several known natural polymorphisms and amino acid changes of unknown significance. All cultivable HSV-2 isolates showed susceptibility to ACV.
ANTIVIRAL RESEARCH
(2022)
