Article
Oncology
Hao Ni, Min Guo, Xuepei Zhang, Lei Jiang, Shuai Tan, Juan Yuan, Huanhuan L. Cui, Yanan Min, Junhao Zhang, Susanne Schlisio, Chunhong Ma, Wangjun Liao, Monica Nister, Chunlin Chen, Shuijie Li, Nailin Li
Summary: In this study, it was found that inhibition of VEGF by Ki8751 suppressed cancer cell proliferation by increasing mitochondrial biogenesis and ROS production. Ki8751 also modulated mitochondrial biogenesis and cancer cell apoptosis by inhibiting the Akt-PGC1 alpha-TFAM signaling pathway.
CANCER BIOLOGY & MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Iryna Kamienieva, Agata Charzynska, Jerzy Duszynski, Dominika Malinska, Joanna Szczepanowska
Summary: Most cases of Parkinson's disease are idiopathic and their causes are unknown. However, a small percentage of cases are caused by genetic mutations, with the parkin gene mutation being the most common. Mitochondrial dysfunction is believed to play a role in both idiopathic and genetic Parkinson's disease. However, different studies have reported inconsistent data on mitochondrial changes, which may be due to the genetic variability of the disease. This study investigates the mitochondrial function and dynamics in fibroblasts from Parkinson's disease patients with parkin mutations. Cluster analysis of the data revealed characteristic features of Parkinson's disease fibroblasts, including smaller and less complex mitochondrial networks, as well as decreased levels of mitochondrial biogenesis regulators and mitophagy mediators.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Review
Neurosciences
Iryna Kamienieva, Jerzy Duszynski, Joanna Szczepanowska
Summary: The familial form of Parkinson's disease is linked to mutations in specific genes, with mutations in the parkin gene being one of the most common causes of early-onset PD. Mitochondrial dysfunction is an emerging active player in the pathology of neurodegenerative diseases, as mitochondria are highly dynamic structures integrated with many cellular functions.
TRANSLATIONAL NEURODEGENERATION
(2021)
Article
Cell Biology
Benjamin Gottschalk, Zhanat Koshenov, Olaf A. Bachkoenig, Rene Rost, Roland Malli, Wolfgang F. Graier
Summary: Endoplasmic reticulum (ER) critically depends on ATP supply for its functions. The disruption of protein trafficking and folding in the ER leads to ER stress and the unfolded protein response (UPR). During ER stress, the stability and lifetime of mitochondrial associated ER membranes (MAM) increase, resulting in an increase in mitochondrial activity and ATP generation, which in turn enhances the ATP supply for the ER. The increased stability and lifetime of MAMs during ER stress rely on the mitochondrial fusion protein Mitofusin2 (MFN2). Knockdown of MFN2 impairs the response of mitochondria to ER stress and reduces ATP supply for the ER.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Jiajia Li, Xiawei Dang, Antonietta Franco, Gerald W. Dorn
Summary: Mitochondrial repair is crucial for metabolic homeostasis and the MFN2 protein plays a key role in regulating mitochondrial fusion and mitophagy. Our study reveals that the phosphorylation state of MFN2 can determine the fate of mitochondria by either promoting fusion or triggering mitophagy. PINK1 kinase is identified as the pivotal regulator of MFN2 functionality, while Parkin is dispensable for MFN2 inactivation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Endocrinology & Metabolism
Kumari Alka, Jay Kumar, Renu A. Kowluru
Summary: In diabetic retinopathy, the downregulation of mitochondrial fusion enzyme Mfn2 leads to disruption of mitochondrial dynamics and dysfunction. This study found that increased acetylation of Mfn2 inhibits its GTPase activity, causes mitochondrial fragmentation, and impairs removal of damaged mitochondria. Therefore, protecting Mfn2 activity could maintain mitochondrial homeostasis and inhibit the development/progression of diabetic retinopathy.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Review
Cell Biology
Xiusheng Chen, Qi Wang, Shihua Li, Xiao-Jiang Li, Weili Yang
Summary: PINK1 is a mitochondrial kinase involved in mitophagy and neuronal protection. Mutations in PINK1 gene can cause early onset Parkinson's disease with mitochondrial dysfunction. Although there is evidence from in vitro studies supporting the role of PINK1 in regulating mitochondrial function, strong in vivo evidence is still lacking. Additionally, PINK1 has functions independent of mitochondria.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Neurosciences
Laura Scott, Senthilkumar S. Karuppagounder, Stewart Neifert, Bong Gu Kang, Hu Wang, Valina L. Dawson, Ted M. Dawson
Summary: In this study, a transgenic model was generated to examine the impact of Parkin loss on mitochondrial function in PolgAD257A/D257A mice. Surprisingly, no dopaminergic neurodegeneration or nigral-striatal neurobehavioral deficits were observed in these mice. These findings suggest a lack of synergism between Parkin loss and mitochondrial dysfunction in this mouse model of mitochondrial deficits.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Catherine Kim, Meredith Juncker, Ryan Reed, Arthur Haas, Jessie Guidry, Michael Matunis, Wei-Chih Yang, Joshua Schwartzenburg, Shyamal Desai
Summary: In cells treated with mitochondrial stressors, SUMOylation of Mfn1/2 facilitates the aggregation of damaged mitochondria at the perinuclear region, potentially through acting as a molecular glue to interact with other proteins.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Chemistry, Medicinal
Olivia A. Lambourne, Shane Bell, Lea P. Wilhelm, Erika B. Yarbrough, Gabriel G. Holly, Oliver M. Russell, Arwa M. Alghamdi, Azeza M. Fdel, Carmine Varricchio, Emma L. Lane, Ian G. Ganley, Arwyn T. Jones, Matthew S. Goldberg, Youcef Mehellou
Summary: Ubiquitin phosphorylation by PINK1 is crucial for mitophagy and potential PD treatments. N (6)-substituted adenosines, like kinetin riboside and N (6)-benzyladenosine, activate PINK1 and induce mitophagy in cells. Moreover, these adenosines can inhibit elevated ubiquitin phosphorylation induced by mitochondrial depolarizing agents.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biology
Jake P. Mann, Xiaowen Duan, Satish Patel, Luis Carlos Tabara, Fabio Scurria, Anna Alvarez-Guaita, Afreen Haider, Ineke Luijten, Matthew Page, Margherita Protasoni, Koini Lim, Sam Virtue, Stephen O'Rahilly, Martin Armstrong, Julien Prudent, Robert K. Semple, David B. Savage
Summary: This study identified a rare genetic mitochondrial dysfunction caused by the MFN2 gene mutation, which results in adipose tissue abnormalities, insulin resistance, and perturbed secretion of adipokines. The findings suggest that selective mitochondrial dysfunction and activation of the integrated stress response in adipose tissue play a role in the pathological adipose remodeling and metabolic disease associated with this mutation.
Review
Biochemistry & Molecular Biology
Hongxu Xian, Yih-Cherng Liou
Summary: This article summarizes the crucial roles of outer mitochondrial membrane proteins in mitochondrial dynamics, quality control, and mitophagy, discussing their functions in maintaining mitochondrial homeostasis and adapting to different contexts. The insights into these proteins in mechanistic research could lead to a better understanding of mitochondrial quality control and its pathological implications.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Chemistry, Medicinal
Runjie Sun, Jiang Liu, Manya Yu, Mengting Xia, Yanyu Zhang, Xiaoqi Sun, Yunsheng Xu, Xing Cui
Summary: This study confirmed the therapeutic effect of paeoniflorin on Bortezomib-induced peripheral neuropathy (BiPN) by reducing IL6 levels and regulating PARKIN-mediated mitochondrial autophagy and mitochondrial damage.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2022)
Article
Spectroscopy
Dingyi Guo, Jie Sun, Minggang Tian, Weiying Lin
Summary: A red-emissive RNA ligand bearing two positive charges was developed to visualize mitochondrial depolarization, and cell damage induced by H2O2 was successfully observed with the probe. The probe has the potential to promote research in mitochondrial membrane potential, cell apoptosis, and related areas.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2021)
Article
Biochemistry & Molecular Biology
Sou Inagaki, Yoshiaki Suzuki, Keisuke Kawasaki, Rubii Kondo, Yuji Imaizumi, Hisao Yamamura
Summary: Mitochondria play a crucial role in cytosolic Ca2+ buffering and energy metabolism. Recent research has shown that Mfn2 regulates Ca2+ signaling by tethering mitochondria and sarco-plasmic reticulum, enhancing mitochondrial function and VSMC proliferation. However, the physiological role of Mfn1 in Ca2+ signaling and mitochondrial function is still unclear.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Nutrition & Dietetics
Debora Basile, Michele Bartoletti, Maurizio Polano, Lucia Bortot, Lorenzo Gerratana, Paola Di Nardo, Matteo Borghi, Valentina Fanotto, Giacomo Pelizzari, Camilla Lisanti, Mattia Garutti, Silvia Buriolla, Elena Ongaro, Eva Andreuzzi, Marcella Montico, Luca Balestreri, Gianmaria Miolo, Giuseppe Toffoli, Giuseppe Aprile, Fabio Puglisi, Angela Buonadonna
Summary: This study investigated the prognostic role of adiposity, especially visceral fat, in patients with metastatic colorectal cancer. The results showed that higher visceral fat values were associated with worse outcomes in these patients. Further research is needed to explore the impact of visceral fat on colorectal cancer patients.
CLINICAL NUTRITION
(2021)
Article
Cell Biology
Maurizio Polano, Emanuele Fabbiani, Eva Adreuzzi, Federica Di Cintio, Luca Bedon, Davide Gentilini, Maurizio Mongiat, Tamara Ius, Mauro Arcicasa, Miran Skrap, Michele Dal Bo, Giuseppe Toffoli
Summary: In this study, a machine learning classification model based on epigenetic data was developed to separate glioma patients according to their immunosuppression state, achieving a best performance of 82.8% accuracy. By selecting genes and improving selection through data-driven procedures, a method to stratify glioma patients based on their epigenomic state was provided.
Article
Biochemistry & Molecular Biology
Albina Fejza, Maurizio Polano, Lucrezia Camicia, Evelina Poletto, Greta Carobolante, Giuseppe Toffoli, Maurizio Mongiat, Eva Andreuzzi
Summary: The study suggests that EMILIN-2 plays a role in the response to PD-L1 inhibitors in melanoma patients, with its absence associated with increased PD-L1 expression and improved immunotherapy efficacy. EMILIN-2 regulates PD-L1 expression in melanoma cells through immune-dependent mechanisms, impacting treatment outcomes and angiogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Barbara Bortot, Maura Apollonio, Gabriele Baj, Laura Andolfi, Luisa Zupin, Sergio Crovella, Matteo di Giosia, Andrea Cantelli, Roberto Saporetti, Luca Ulfo, Annapaola Petrosino, Giovanni Di Lorenzo, Federico Romano, Giuseppe Ricci, Maurizio Mongiat, Alberto Danielli, Matteo Calvaresi, Stefania Biffi
Summary: This study proposes a bacteriophage-based receptor targeted photodynamic therapy for treating EGFR-positive ovarian cancer. The modified M13 bacteriophage with an EGFR binding peptide displayed on its surface effectively kills cancer cells through ROS generation by photosensitizers. It also downregulates EGFR expression and induces autophagy.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Oncology
Eva Andreuzzi, Albina Fejza, Maurizio Polano, Evelina Poletto, Lucrezia Camicia, Greta Carobolante, Giulia Tarticchio, Federico Todaro, Emma Di Carlo, Melania Scarpa, Marco Scarpa, Alice Paulitti, Alessandra Capuano, Vincenzo Canzonieri, Stefania Maiero, Mara Fornasarig, Renato Cannizzaro, Roberto Doliana, Alfonso Colombatti, Paola Spessotto, Maurizio Mongiat
Summary: This study reveals the importance of EMILIN-2 in the development and prognosis of colorectal cancer. Loss of EMILIN-2 is associated with increased tumor numbers and altered immune cell populations in CRC models. Mechanistically, EMILIN-2 regulates macrophage polarization through the Toll-like Receptor 4/MyD88/NF-kappa B pathway. Furthermore, EMILIN-2 expression levels are correlated with the prognosis of CRC patients.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Eliana Pivetta, Alessandra Capuano, Maddalena Vescovo, Eugenio Scanziani, Roberto Doliana, Maurizio Mongiat, Paola Spessotto, Andrea Vecchione, Andrea Cappelleri, Gian Luca Rampioni Vinciguerra
Summary: Alterations in ECM components, such as loss of EMILIN-1, can lead to changes in the inflammatory environment in the skin and affect the development of psoriasis. Deficiency of EMILIN-1 impairs macrophage polarization and disrupts tissue homeostasis.
Article
Biochemistry & Molecular Biology
Stefano Barbera, Luisa Raucci, Giusy Tassone, Laura Tinti, Filippo Prischi, Annalisa Santucci, Maurizio Mongiat, Gian Marco Tosi, Federico Galvagni, Anna Dimberg, Cecilia Pozzi, Maurizio Orlandini
Summary: Blocking the signaling activated by the plasma membrane receptor CD93 has been shown to be useful in antiangiogenic treatment and oncotherapy. CD93 structurally exists as a dimer in endothelial cells and its oligomeric form is important for binding to its ligand Multimerin-2. Crystallographic analysis reveals the role of the C-type lectin-like and sushi-like domains in achieving a functional binding state, which provides valuable information for the development of drugs targeting CD93 in neovascular pathologies.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Albina Fejza, Lucrezia Camicia, Greta Carobolante, Evelina Poletto, Alice Paulitti, Giorgia Schinello, Emanuele Di Siena, Renato Cannizzaro, Renato V. Iozzo, Gustavo Baldassarre, Eva Andreuzzi, Paola Spessotto, Maurizio Mongiat
Summary: Angiogenesis is a complex process regulated by various factors. This study reveals the significant role of Emilin2 in pericyte physiology and vascular stabilization. Emilin2 affects multiple mechanisms involved in pericyte recruitment and vascular stability. The findings suggest that Emilin2 could be a promising marker for predicting the clinical outcome of patients with melanoma, ovarian, and potentially other forms of cancer.
Review
Immunology
Albina Fejza, Greta Carobolante, Evelina Poletto, Lucrezia Camicia, Giorgia Schinello, Emanuele Di Siena, Giuseppe Ricci, Maurizio Mongiat, Eva Andreuzzi
Summary: Immune-checkpoint inhibitors (ICIs) are important in cancer therapy, but the long-lasting therapeutic effect is only seen in a minority of patients. Therefore, finding predictive biomarkers for responsiveness to ICIs is crucial. This review systematically evaluates the literature on the relation between extracellular matrix (ECM) and ICIs efficacy, highlighting the use of ECM-derived proteolytic products as liquid biopsy-based biomarkers.
FRONTIERS IN IMMUNOLOGY
(2023)
Meeting Abstract
Oncology
Barbara Montico, Giorgio Giurato, Roberto Guerrieri, Annamaria Salvati, Francesca Colizzi, Lorena Baboci, Luca Sigalotti, Alessia Covre, Michele Maio, Agostino Steffan, Tuula A. Nyman, Alessandro Weisz, Maurizio Mongiat, Eva Andreuzzi, Elisabetta Fratta
Article
Medicine, Research & Experimental
Mara Fornasarig, Alessandra Capuano, Stefania Maiero, Eliana Pivetta, Vincenzo Canzonieri, Claudio Belluco, Maurizio Mongiat, Renato Cannizzaro, Paola Spessotto
Summary: This study found abnormal changes in vasculature in patients with Linitis plastica (LP) using probe-based Confocal Laser Endomicroscopy (pCLE). The abnormal features included vessel enlargement, tortuosity, and leakage associated with the affected submucosal layer. This provides a new endoscopic approach and strategy for diagnosing LP.
CLINICAL AND EXPERIMENTAL MEDICINE
(2023)
Meeting Abstract
Gastroenterology & Hepatology
E. Andreuzzi, A. Fejza, E. Poletto, L. Camicia, G. Carobolante, M. Polano, E. Di Carlo, M. Scarpa, S. Maiero, M. Fornasarig, R. Cannizzaro, M. Mongiat
DIGESTIVE AND LIVER DISEASE
(2022)
Meeting Abstract
Gastroenterology & Hepatology
M. Fornasarig, A. Capuano, S. Maiero, E. Pivetta, G. Guarnieri, R. Magris, V Canzonieri, M. Mongiat, R. Cannizzaro, P. Spessotto
DIGESTIVE AND LIVER DISEASE
(2021)