Article
Dentistry, Oral Surgery & Medicine
Z. Wang, F. Zhou, X. Feng, H. Li, C. Duan, Y. Wu, Y. Xiong
Summary: Periodontitis, a common chronic oral disease, is highly susceptible to aging. FoxO1, a transcription factor involved in body development and senescence, was found to play a role in halting the progression of age-related alveolar bone loss in mice. Further studies revealed that FoxO1 deficiency enhanced NLRP3 inflammasome signaling in osteoblasts, and inhibiting NLRP3 inflammasome rescued osteoblast differentiation under oxidative stress. These findings provide insights into the role of FoxO1 and suggest a potential mechanism for treating age-related alveolar bone loss.
JOURNAL OF DENTAL RESEARCH
(2023)
Article
Cell Biology
Yulong Wang, Li Ou, Xirong Li, Tingyu Zheng, Wei-pei Zhu, Ping Li, Lijun Wu, Tianlan Zhao
Summary: POLRMT is significantly elevated in skin squamous cell carcinoma (SCC) and its inhibition has anti-tumor effects in SCC cells, affecting mitochondrial functions and inducing cell apoptosis.
CELL DEATH DISCOVERY
(2022)
Article
Biochemistry & Molecular Biology
Youssef A. Hegazy, Sara C. Cloutier, Sagar M. Utturkar, Subhadeep Das, Elizabeth J. Tran
Summary: This study used transient-transcriptome sequencing (TT-seq) to investigate the correlation of sense/antisense pairs in a dbp2 & UDelta; strain and found over 700 sense/antisense pairs, including PHO84, to be positively correlated, challenging the prevailing model. Further experiments revealed that the 3' untranslated region (3'UTR) of PHO84 plays a repressive role in sense expression independently of antisense transcripts. Genetic screening also identified factors linked to negative regulation in the 3'UTR-dependent repression of PHO84. Additionally, the study showed that the PHO84 promoter and terminator form gene loops, which correlate with transcriptional repression, and the RNA-binding protein Tho1 enhances this looping and the 3'UTR-dependent repression.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Gastroenterology & Hepatology
Liuyi Hao, Wei Zhong, Haibo Dong, Wei Guo, Xinguo Sun, Wenliang Zhang, Ruichao Yue, Tianjiao Li, Alexandra Griffiths, Ali Reza Ahmadi, Zhaoli Sun, Zhenyuan Song, Zhanxiang Zhou
Summary: The study reveals that hepatic ATF4 plays a pathological role in alcohol-induced mitochondrial dysfunction and liver injury by disrupting the NRF1-TFAM pathway. In patients with alcoholic liver disease, the activation of ATF4 is associated with mitochondrial dysfunction. Knocking out ATF4 or overexpressing TFAM can alleviate alcohol-induced liver damage. This is achieved through the negative regulation of TFAM expression by ATF4, affecting ethanol-mediated mitochondrial dysfunction and cell death.
Article
Cell Biology
Xiaojun Li, Linya Yao, Tao Wang, Xiaolei Gu, Yufan Wu, Ting Jiang
Summary: Overexpressed POLRMT is associated with the development and poor survival of prostate cancer. Depletion of POLRMT impairs mitochondrial functions and induces oxidative stress and apoptosis in prostate cancer cells. Moreover, overexpression of POLRMT enhances the proliferation and migration of prostate cancer cells.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Jia Guo, Feng Zhou, Zhi Liu, Yuan Cao, Wanming Zhao, Zheru Zhang, Qiming Zhai, Yan Jin, Bei Li, Fang Jin
Summary: Combining exosomes with dental pulp stem cells (DPSCs) has a remarkable effect on bone regeneration. Exosomes promote osteogenic differentiation of DPSCs by transferring mitochondrial transcription factor A (TFAM) mRNA and enhancing glutamate metabolism and oxidative phosphorylation (OXPHOS) activity. This study provides a new potential strategy to improve DPSC-based bone regenerative treatment.
CELL PROLIFERATION
(2022)
Review
Cell Biology
Astrid S. Pfister
Summary: Nucleolar stress is caused by a dysfunction in ribosome biogenesis and defective nucleolar architecture. It can be triggered by various factors, such as mutation of ribosomal proteins, inhibition of RNA polymerase I, and intracellular or ectopic stress. Nucleolar stress has both pathological and therapeutic implications, as it is linked to diseases like neurodegeneration and cancer, but can also be used to target p53-mutated tumors for anti-cancer therapy. The involvement of nucleolar stress in autophagy and its transcriptional regulation are still under investigation, but show potential for future therapeutic applications.
Article
Biochemistry & Molecular Biology
Stephen P. Burr, Florian Klimm, Angelos Glynos, Malwina Prater, Pamella Sendon, Pavel Nash, Christopher A. Powell, Marie-Lune Simard, Nina A. Bonekamp, Julia Charl, Hector Diaz, Lyuba V. Bozhilova, Yu Nie, Haixin Zhang, Michele Frison, Maria Falkenberg, Nick Jones, Michal Minczuk, James B. Stewart, Patrick F. Chinnery
Summary: Mitochondrial activity varies between organs, and lineage-specific expression profiles of essential mitochondrial genes emerge early in mouse development. Disrupting intra-mitochondrial protein synthesis with mtDNA mutations induces cell lineage-specific compensatory responses, including novel molecular pathways not previously associated with organellar maintenance. These compensatory pathways, regulated by transcription factors promoting organelle resilience, contribute to tissue specificity in mitochondrial diseases and may be potential targets for organ-directed treatments.
Article
Multidisciplinary Sciences
Yeawon Kim, Chuang Li, Chenjian Gu, Yili Fang, Eric Tycksen, Anuradhika Puri, Terri A. Pietka, Jothilingam Sivapackiam, Kendrah Kidd, Sun-Ji Park, Bryce G. Johnson, Stanislav Kmoch, Jeremy S. Duffield, Anthony J. Bleyer, Meredith E. Jackrel, Fumihiko Urano, Vijay Sharma, Maria Lindahl, Ying Maggie Chen
Summary: Research shows that mesencephalic astrocyte-derived neurotrophic factor can improve defective autophagy/mitophagy and decrease renal scarring in ADTKD.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Kyle A. Hubble, Michael F. Henry
Summary: By studying the TACO1 orthologue in yeast, it was found that this protein is a general mitochondrial translation factor rather than a specific translational activator. Its activity is necessary for optimal expression of mitochondrial DNA reporters, indicating a general role in mitochondrial translation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Joyce Yip, Suqing Wang, Jasper Tan, Teck Kwang Lim, Qingsong Lin, Zhang Yu, Ofri Karmon, Ophry Pines, Norbert Lehming
Summary: The Krebs cycle enzyme fumarase is involved in DNA damage response by protecting the desulfurase Nfs1p in mitochondria from modification and inactivation. Overexpression of Nfs1p can enhance DNA repair enzyme activity and compensate for the lack of fumarase.
Article
Biochemistry & Molecular Biology
Zhenxing Zhang, Chao Chen, Fan Yang, Yi-Xin Zeng, Pengkai Sun, Ping Liu, Xinjian Li
Summary: A study has found that itaconate, an endogenous metabolite, functions as a lysosomal inducer in macrophages during bacterial infection. It activates the transcription factor TFEB by directly alkylating it, leading to increased lysosomal biogenesis and improved antibacterial ability. Inhibition of itaconate synthesis or expression of a mutant TFEB lacking alkylation impairs macrophage's antibacterial ability, while treatment with a cell-permeable itaconate derivative limits inflammation.
Article
Cell Biology
Douja Chamseddine, Siraje A. Mahmud, Aundrea K. Westfall, Todd A. Castoe, Rance E. Berg, Mark W. Pellegrino
Summary: ATF5 protects the host from enteric pathogens by maintaining the integrity of the intestinal barrier and preventing dysregulated glucose metabolism associated with obesity and hyperglycemia. It supports intestinal barrier function by promoting a satiety response through transcriptional regulation of cholecystokinin.
Article
Biochemistry & Molecular Biology
Anqi Li, Meng Gao, Bilin Liu, Yuan Qin, Lei Chen, Hanyu Liu, Guohua Gong
Summary: This study investigated the impact of oxidative stress on the differentiation and development of iPS-CMs and found that mitochondrial-targeted antioxidant can improve the maturation of iPS-CMs.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Lei Sun, Arabella Wan, Zhuolong Zhou, Dongshi Chen, Heng Liang, Chuwei Liu, Shijia Yan, Yi Niu, Ziyou Lin, Siyue Zhan, Shanfeng Wang, Xianzhang Bu, Weiling He, Xiongbin Lu, Anlong Xu, Guohui Wan
Summary: The study identified an RNA-binding protein RALY as a critical regulator in colorectal cancer metabolism, promoting the post-transcriptional processing of miRNAs that downregulate metabolism-associated genes and reprogram mitochondrial metabolism in cancer cells. Increased levels of RALY were associated with poor prognosis in CRC patients expressing low levels of mitochondrion-associated genes, and this effect was facilitated by N6-methyladenosine switch under reactive oxygen species stress. Inhibition of m6A methylation abolished RALY recognition of pri-miRNAs, leading to inhibition of colorectal tumor growth and progression both in vivo and in organoid models.
Article
Biochemistry & Molecular Biology
Elena Britti, Fabien Delaspre, Jordi Tamarit, Joaquim Ros
Summary: This study explored the role of calpains in Friedreich Ataxia, revealing that calpain inhibitors can enhance NCLX levels, protect sensory neurons, and restore mitochondrial function. These findings suggest a central role for calcium homeostasis and calpains in the neurodegeneration of frataxin-deficient dorsal root ganglia neurons.
NEUROCHEMICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Elena Britti, Fabien Delaspre, Arabela Sanz, Marta Medina-Carbonero, Marta Llovera, Rosa Purroy, Stefka Mincheva-Tasheva, Jordi Tamarit, Joaquim Ros
Summary: Calcitriol supplementation can reverse the molecular and cellular markers altered in DRG neurons due to frataxin deficiency, restore mitochondrial function, and improve cell survival.
BIOCHEMICAL JOURNAL
(2021)
Article
Neurosciences
Laura Rodriguez-Pascau, Elena Britti, Pablo Calap-Quintana, Yi Na Dong, Cristina Vergara, Fabien Delaspre, Marta Medina-Carbonero, Jordi Tamarit, Federico V. Pallardo, Pilar Gonzalez-Cabo, Joaquim Ros, David R. Lynch, Marc Martinell, Pilar Pizcueta
Summary: Friedreich ataxia (FRDA) is characterized by degeneration of large sensory neurons and spinocerebellar tracts, as well as cardiomyopathy and increased incidence in diabetes. The peroxisome proliferator-activated receptor gamma (PPAR gamma) pathway plays a key role in the pathogenesis of FRDA, with leriglitazone potentially providing an effective therapy by targeting this pathway to improve mitochondrial function and biogenesis. Leriglitazone has shown promising results in cellular and animal models, indicating its potential as a treatment for FRDA.
NEUROBIOLOGY OF DISEASE
(2021)
Review
Biochemistry & Molecular Biology
Jordi Tamarit, Elena Britti, Fabien Delaspre, Marta Medina-Carbonero, Arabela Sanz-Alcazar, Elisa Cabiscol, Joaquim Ros
Summary: This review discusses how iron and calcium dyshomeostasis impacts cellular functions, and suggests strategies for finding an effective therapy for Friedreich Ataxia, a neuro-cardiodegenerative disease caused by frataxin deficiency.
Article
Agriculture, Dairy & Animal Science
Maria Alba Sorolla, Marta Marques, Eva Parisi, Anabel Sorolla
Summary: In this study, a novel gene Nrf1 was discovered to play a crucial role in embryonic development. Through gene screening, Nrf1 was identified to regulate the activation and deactivation of other genes. Additionally, an ENU mutagenesis screen was established to identify new genes involved in epigenetic regulation in mammals.
Article
Biochemistry & Molecular Biology
Marta Medina-Carbonero, Arabela Sanz-Alcazar, Elena Britti, Fabien Delaspre, Elisa Cabiscol, Joaquim Ros, Jordi Tamarit
Summary: Friedreich Ataxia is a rare neuro-cardiodegenerative disease caused by mutations in the frataxin gene. The most common mutation is a GAA expansion in the first intron of the gene, resulting in decreased frataxin expression. By introducing a specific mutation into the murine Fxn gene, researchers have analyzed the consequences of this mutation in vivo. They found that mice with this mutation displayed low frataxin levels in all tissues, neurological deficits resembling those in FA patients, and mitochondrial alterations. The researchers concluded that the primary pathological mechanism underlying this mutation is frataxin deficiency, suggesting frataxin replacement therapies may benefit patients with this mutation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Oncology
Maria Alba Sorolla, Ivan Hidalgo, Anabel Sorolla, Robert Montal, Ona Pallise, Antonieta Salud, Eva Parisi
Summary: Colorectal cancer is associated with a high mortality rate, and oxidative stress has been linked to its initiation and progression. ROS play diverse roles in cancer, and ROS-modulating agents may have therapeutic potential for cancer patients.
Article
Oncology
Marta Marques, Maria Alba Sorolla, Izaskun Urdanibia, Eva Parisi, Ivan Hidalgo, Serafin Morales, Antonieta Salud, Anabel Sorolla
Summary: Triple negative breast cancer is a challenging type of breast cancer to treat due to the difficulty in inhibiting transcription factors, which play a crucial role in its growth. This article outlines the recent advances and strategies in targeting these transcription factors, as well as their potential as clinical biomarkers. The research in this field is likely to continue evolving.
Article
Oncology
Maria Mulet, Ruben Osuna-Gomez, Carlos Zamora, Jose M. Porcel, Juan C. Nieto, Lidia Perea, Virginia Pajares, Ana M. Munoz-Fernandez, Nuria Calvo, Maria Alba Sorolla, Silvia Vidal
Summary: This study provides novel information about the role of neutrophils in malignant pleural effusion (MPE) and their clinical relevance. Neutrophils contribute to tumor progression through the release of neutrophil extracellular traps (NETs) and are associated with worse outcomes in lung adenocarcinoma patients with MPE.
Article
Biochemistry & Molecular Biology
Rui Alves, Maria Pazos-Gil, Marta Medina-Carbonero, Arabela Sanz-Alcazar, Fabien Delaspre, Jordi Tamarit
Summary: This study analyzed the conservation of structure and residues among frataxins and CyaY proteins, identifying four highly conserved residue clusters, with cluster 3 unique to eukaryotic frataxins and CyaY proteins from the Rickettsia genus. The tyrosine residue in cluster 3 is hypothesized to prevent the formation of reactive oxygen species during iron detoxification.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Isabel C. Lopez-Mejia, Jordi Pijuan, Raul Navaridas, Maria Santacana, Sonia Gatius, Ana Velasco, Gerard Castella, Anais Panosa, Elisa Cabiscol, Miquel Pinyol, Laura Coll, Nuria Bonifaci, Laura Plata Pena, August Vidal, Alberto Villanueva, Eloi Gari, David Llobet-Navas, Lluis Fajas, Xavier Matias-Guiu, Andree Yeramian
Summary: Uterine serous carcinoma (USC) is a highly metastatic and fatal form of endometrial cancer (EC). This study identified focal adhesion kinase (FAK) as a highly activated tyrosine kinase in USC and showed that targeting FAK can inhibit cell growth and reduce migration in USC cell lines. The study also revealed that oxidative stress is increased in USC tumors compared to endometrioid endometrial carcinoma (EEC), and ROS-mediated FAK activation plays a role in cell migration and poor prognosis in USC.
MOLECULAR ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Eva Parisi, Ivan Hidalgo, Robert Montal, Ona Pallise, Jordi Tarragona, Anabel Sorolla, Anna Novell, Kyra Campbell, Maria Alba Sorolla, Andreu Casali, Antonieta Salud
Summary: In this study, a genetic screen identified 13 new genes that modified circulating tumor cell numbers in a whole animal CRC model. Evaluation of candidate genes at the gene expression level in both internal and independent human CRC cohorts revealed that low expression of PLA2G12A correlated with poor clinical outcomes. Further analysis showed that low expression of PLA2G12A was enriched in epithelial-mesenchymal transition signatures. Functional validation using colon cancer cell lines demonstrated that PLA2G12A deficiency increased cell proliferation, migration, and invasion. Overall, this study identifies PLA2G12A as a prognostic biomarker for early-stage CRC and provides evidence for its role in tumor growth and dissemination.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Mariona Pont, Marta Marques, Maria Alba Sorolla, Eva Parisi, Izaskun Urdanibia, Serafin Morales, Antonieta Salud, Anabel Sorolla
Summary: CRISPR technology has revolutionized cancer research, particularly in the field of breast cancer and triple negative breast cancer (TNBC). It allows scientists to model these diseases more effectively, discover unknown genes involved in cancer progression, improve early and sensitive diagnosis, and explore more selective and efficient treatments. Scientists are currently exploring different methods to optimize the distribution of CRISPR components in tumors. However, CRISPR technology also has limitations and future directions for improvement.
Letter
Respiratory System
Jose M. Porcel, Anabel Sorolla, Eva Parisi, Silvia Bielsa, Antonieta Salud, M. Alba Sorolla
ANNALS OF THE AMERICAN THORACIC SOCIETY
(2022)