Article
Biochemistry & Molecular Biology
James H. Schofield, Zachary T. Schafer
Summary: The relationship between mitophagy and ROS production is complex and not fully understood. This review discusses mtROS generation and their detrimental effects on cellular viability, along with the cellular defense mechanisms against oxidative stress. Furthermore, the prominent mechanisms governing mitophagy induction that bear on oxidative stress are explored.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
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)
Review
Immunology
Miranda D. Chavez, Hubert M. Tse
Summary: Mitochondrial dysfunction and oxidative stress are associated with T cell-mediated autoimmune diseases, and targeting metabolic pathways can inhibit autoreactive T cell activation. Increasing the requirements of Tregs for ROS and oxidative phosphorylation can promote self-tolerance and inhibit the activity of autoreactive T cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Jianli Ma, Junwen Zhu, Jingtong Li, Ji Liu, Xiaofeng Kang, Jinming Yu
Summary: Radiotherapy has demonstrated efficacy in breast cancer, but resistance remains a challenge. Mitochondria, as a crucial regulator of redox homeostasis, have emerged as a target for radiotherapy. This study identified ENO1 as a prognostic marker for radiotherapy efficacy in breast cancer. ENO1 reduces reactive oxygen species and apoptosis through modulation of mitochondrial homeostasis, leading to radiotherapeutic resistance. LINC00663 was identified as an upstream regulator of ENO1, and its downregulation enhances radiotherapeutic sensitivity in breast cancer by regulating ENO1 protein stability.
Article
Biochemistry & Molecular Biology
Hiromu Ito, Hiromi Kurokawa, Hirofumi Matsui
Summary: Mitochondria, essential organelles for energy production in eukaryotes, generate reactive oxygen species during the process which play pivotal roles in cell signaling and iron homeostasis regulation. The regulation of iron transportation, involving proteins like HCP1, DMT1, and mitoferrin, is increasingly understood in relation to mitochondrial reactive oxygen species and diseases.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Multidisciplinary Sciences
Ivan Menendez-Montes, Salim Abdisalaam, Feng Xiao, Nicholas T. Lam, Shibani Mukherjee, Luke I. Szweda, Aroumougame Asaithamby, Hesham A. Sadek
Summary: Mitochondrial utilization of fatty acids induces a significant increase in ROS detection at the chromatin level, indicating that mitochondrial metabolic perturbations directly alter the nuclear redox status, with chromatin being particularly sensitive to the prooxidant effect of FA utilization by the mitochondria.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Remi Hatinguais, Arnab Pradhan, Gordon D. Brown, Alistair J. P. Brown, Adilia Warris, Elena Shekhova
Summary: This study highlights the crucial role of mitochondrial ROS (mitoROS) in macrophage antifungal responses, specifically in the regulation of cytokine secretion through RET-mediated mitoROS production. Furthermore, NOX2 is demonstrated to be essential for regulating cytokine secretion by RET-associated mitoROS in response to infection with swollen conidia.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biology
Barbara E. Corkey
Summary: Changes correlating with increasing obesity include insulin resistance, hyperlipidaemia, hyperinsulinaemia, highly processed food and environmental toxins including plastics and air pollution. The hypothesis is that substances that have entered our bodies recently cause obesity by generating false and misleading information about energy status. Examples are provided of food additives that generate reactive oxygen species and impact redox state, thereby eliciting inappropriate tissue-specific functional changes, including insulin secretion. Reversal requires identification, neutralization, or removal of these compounds.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Michael O. Isei, Don Stevens, Collins Kamunde
Summary: The research found that heart mitochondria show different responses to copper and thermal stress, and the consumption capacity of H2O2 is influenced by the type of substrate, temperature, and copper. The NADPH-dependent peroxidase system is the centerpiece of ROS scavenging in heart mitochondria, and copper has the ability to inhibit specific mitochondrial ROS scavenging pathways.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Lindsay E. Volk, Constantine D. Mavroudis, Tiffany Ko, Thomas Hallowell, Nile Delso, Anna L. Roberts, Jonathan Starr, William Landis, Yuxi Lin, Marco Hefti, Ryan W. Morgan, Richard W. Melchior, Tami M. Rosenthal, Alexander Chappell, Douglas Fisher, Molly Dreher, Daniel J. Licht, Jonathan Chen, J. William Gaynor, Christopher E. Mascio, Todd J. Kilbaugh
Summary: The study found that using cardiopulmonary bypass during cardiac surgery can lead to decreased cerebral mitochondrial respiration even in the absence of local markers of ischemia. Exposure to 4 hours of cardiopulmonary bypass resulted in a significant increase in cerebral mitochondrial reactive oxygen species formation.
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
(2021)
Article
Biochemistry & Molecular Biology
Parsa Alan, Kurt R. Vandevoorde, Bharat Joshi, Ben Cardoen, Guang Gao, Yahya Mohammadzadeh, Ghassan Hamarneh, Ivan R. Nabi
Summary: Mitochondria are a major source of reactive oxygen species (ROS) that are cytotoxic and contribute to cancer progression when uncontrolled. This study investigated the mechanisms underlying mitophagic control of mitochondrial homeostasis, and found that the E3 ubiquitin ligase Gp78 plays a role in promoting both basal and damage-induced mitophagy. Knockout of Gp78 increased mitochondrial volume and ROS production, and rendered cells resistant to mitophagy. This study highlights the importance of maintaining a healthy mitochondrial population in limiting ROS production and tumor cell proliferation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Hao Heng, Gang Song, Xuetong Cai, Jian Sun, Ke Du, Xiaoran Zhang, Xia Wang, Fude Feng, Shu Wang
Summary: In this study, a strategy for environment-responsive in situ synthesis of molecular fluorescent dyes was developed. The efficient synthesis of cyanine dyes was achieved using a photoextension strategy, and the potential application in cancer cells was explored. The results showed preferential cyanine expression in cancer cells, making it a promising approach for cancer imaging and therapy.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Salvatore Antonucci, Moises Di Sante, Federica Tonolo, Laura Pontarollo, Valeria Scalcon, Petra Alanova, Roberta Menabo, Andrea Carpi, Alberto Bindoli, Maria Pia Rigobello, Marco Giorgio, Nina Kaludercic, Fabio Di Lisa
Summary: The study demonstrates the crucial role of monoamine oxidases (MAOs) in oxidative stress and mitochondrial dysfunction in doxorubicin cardiomyopathy. Pharmacological inhibition of MAOs can alleviate the dysfunctions leading to cell death.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Article
Biochemistry & Molecular Biology
Ryan J. Mailloux
Summary: Mitochondria primarily produce superoxide and hydrogen peroxide, with the latter being considered the main ROS emitted into the cell. While H2O2 is now recognized as a central component in redox signaling, it has been suggested that superoxide may also act as a signal in mammalian cells.
Article
Cardiac & Cardiovascular Systems
Takuya Koizumi, Masaya Watanabe, Takashi Yokota, Masumi Tsuda, Haruka Handa, Jiro Koya, Kotaro Nishino, Daishiro Tatsuta, Hiroyuki Natsui, Takahide Kadosaka, Taro Koya, Motoki Nakao, Hikaru Hagiwara, Rui Kamada, Taro Temma, Shinya Tanaka, Toshihisa Anzai
Summary: Recent studies have shown that sodium-glucose co-transporter-2 inhibitors (SGLT2-i) can reduce the risk of atrial fibrillation (AF) in patients with diabetes mellitus (DM) by reducing oxidative stress. This study aimed to further investigate the mechanisms behind this protective effect and found that empagliflozin, a type of SGLT2-i, can suppress mitochondrial ROS generation and mitigate fibrosis in diabetic rats. These findings suggest that empagliflozin may have a cardioprotective effect by reducing mitochondrial ROS through AMPK signaling pathways and potentially preventing the development of AF in patients with type 2 DM.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Gastroenterology & Hepatology
A. Raquel Esteves, Mario F. Munoz-Pinto, Daniela Nunes-Costa, Emanuel Candeias, Diana F. Silva, Joao D. Magalhaes, A. Raquel Pereira-Santos, I. Luisa Ferreira, Susana Alarico, Igor Tiago, Nuno Empadinhas, Sandra Morais Cardoso
Summary: This study aims to demonstrate that the effects of microbial toxin BMAA in the gut may trigger some cases of PD, and it can spread from the gut to the brain, leading to the development of PD. This finding is crucial for understanding the pathological progression of PD.
Review
Microbiology
Sara Goncalves, Daniela Nunes-Costa, Sandra Morais Cardoso, Nuno Empadinhas, John David Marugg
Summary: Serotonin is a vital compound found in animals, plants, and bacteria. It plays critical roles in regulating body functions and its depletion is associated with neurological disorders in humans. Investigating the biosynthetic pathways of serotonin in bacteria, which may serve as a potential source of serotonin, could lead to important discoveries and the development of new therapeutic strategies.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
David Vicente-Zurdo, Noelia Rosales-Conrado, M. Eugenia Leon-Gonzalez, Leonardo Brunetti, Luca Piemontese, A. Raquel Pereira-Santos, Sandra M. Cardoso, Yolanda Madrid, Silvia Chaves, M. Amelia Santos
Summary: Alzheimer's disease (AD) is a serious and prevalent neurodegenerative disorder for which there is no cure. Recent research has focused on developing multi-target compounds for anti-AD drugs. In this study, seven novel RIV-BIM hybrids were developed and studied. These hybrids combine the active part of the drug rivastigmine with isomeric hydroxyphenylbenzimidazole units. The hybrids showed inhibition of cholinesterases, inhibition of amyloid beta-peptide aggregation, antioxidation, and metal chelation. They also demonstrated good capacity to promote cell viability and neuroprotection. Therefore, the RIV-BIM hybrids have the potential to be drug candidates for AD with multi-target abilities.
Review
Neurosciences
Helena Nunes Costa, Ana Raquel Esteves, Nuno Empadinhas, Sandra Morais Cardoso
Summary: The perception of sporadic Parkinson's disease has significantly changed in recent decades. It is now recognized as a multiorgan and multisystemic pathology that arises from the interaction of susceptible genetic factors with a challenging environment during aging-related decline.
NEUROSCIENCE BULLETIN
(2023)
Article
Neurosciences
Joao D. Magalhaes, Sandra Morais Cardoso
Summary: Parkinson's disease (PD) is a neurodegenerative disease characterized by aSyn accumulation and neuro-inflammatory response. The mitocentric view suggests that mitochondrial dysfunction plays a crucial role in PD pathogenesis. Recent studies provide insights into the mitochondria-inflammation axis in PD etiology, although the mechanisms and effects of aSyn on mitochondrial and cellular dysfunction still need further investigation.
CURRENT OPINION IN NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Joao D. Magalhaes, Ana Raquel Esteves, Emanuel Candeias, Diana F. F. Silva, Nuno Empadinhas, Sandra Morais Cardoso
Summary: Mitochondria, which evolved from an endosymbiotic association, play a crucial role in regulating host metabolism, immunity, and cellular homeostasis. They share certain features with bacteria, known as mitochondrial-derived damage-associated molecular patterns (DAMPs), and their activities can be modulated by extracellular bacteria. In this study, it was found that mesencephalic neurons exposed to an environmental alphaproteobacterium activate innate immunity and show increased expression and aggregation of alpha-synuclein, which interacts with mitochondria, leading to dysfunction. These findings provide insights into the interaction between bacteria and neuronal mitochondria in triggering neuronal damage and neuroinflammation, and the role of bacterial-derived pathogen-associated molecular patterns (PAMPs) in Parkinson's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
David Vicente-Zurdo, Leonardo Brunetti, Luca Piemontese, Beatriz Guedes, Sandra M. Cardoso, Daniel Chavarria, Fernanda Borges, Yolanda Madrid, Silvia Chaves, M. Amelia Santos
Summary: A series of Rivastigmine-Benzimidazole (RIV-BIM) hybrids were found to have multitarget effects in combating Alzheimer's disease (AD). They exhibited antioxidant activity, acted as cholinesterase inhibitors, inhibited amyloid-beta aggregation, and chelated redox-active biometal ions. Furthermore, they showed remarkable inhibitory activity against monoamine oxidases and neuroprotective effects in human neuroblastoma cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Beatriz F. S. Guedes, Sandra Morais Cardoso, Ana Raquel Esteves
Summary: Parkinson's Disease (PD), the second most common neurodegenerative disorder, is characterized by severe loss of dopaminergic neurons and the presence of Lewy bodies. Non-motor symptoms, such as gastrointestinal dysfunction, may occur before motor symptoms. Studies have shown that gut microbiota, which is altered in PD patients, can influence the function of the nervous system. Altered expression of miRNAs, which regulate key mechanisms in PD, has also been observed in PD patients. The bidirectional interaction between gut microbiota and miRNAs may provide insights into the pathogenesis of gut-first PD and the development of biomarkers or therapeutic targets.
Article
Cell Biology
Daniela Marinho, Ildete Luisa Ferreira, Ricardo Lorenzoni, Sandra M. Cardoso, Isabel Santana, A. Cristina Rego
Summary: This study evaluates the efficacy of inhibiting or reducing histone deacetylases (HDACs) in Alzheimer's disease (AD) models by modifying gene transcription. The results show that inhibiting class I HDACs can ameliorate ER-mitochondria cross-talk in AD by normalizing calcium signaling between the two organelles. The selective HDAC inhibitor, Tacedinaline (Tac), counteracted the impaired ER-mitochondria communication and reduced amyloid beta levels in AD cells and animal models. These findings suggest that transcriptional regulation of ER-mitochondria communication could be a promising target for innovative therapeutics in AD.
Article
Biochemistry & Molecular Biology
A. Raquel Esteves, Diana F. Silva, Diogo Banha, Emanuel Candeias, Beatriz Guedes, Sandra M. Cardoso
Summary: Sporadic Parkinson's disease (sPD) is a complex multifactorial disorder with unknown etiology. Our study reveals that lipopolysaccharide (LPS)-induced activation of innate immunity requires functional mitochondria and mimics PD pathology in cells. We also demonstrate that a-synuclein overproduction is an innate immune response, and mitochondria play a crucial role in innate immunity activation in idiopathic PD.
Meeting Abstract
Medicine, General & Internal
S. M. Cardoso, N. Empadinhas
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2022)
Correction
Biochemistry & Molecular Biology
Siew Chin Chan, Chih-Wei Tung, Chia-Wei Lin, Yun-Shiuan Tung, Po-Min Wu, Pei-Hsun Cheng, Chuan-Mu Chen, Shang-Hsun Yang
FREE RADICAL BIOLOGY AND MEDICINE
(2024)
Article
Biochemistry & Molecular Biology
Suyuan Liu, Meiling Tan, Jiangxue Cai, Chenxuan Li, Miaoxin Yang, Xiaoxiao Sun, Bin He
Summary: This study reveals that the antibiotic doxycycline effectively inhibits NLRP3 inflammasome activation by targeting mitochondrial translation and mtDNA synthesis, offering potential for the treatment of NLRP3-related diseases.
FREE RADICAL BIOLOGY AND MEDICINE
(2024)
Article
Biochemistry & Molecular Biology
Hao Liu, Nana Li, Ge Kuang, Xia Gong, Ting Wang, Jun Hu, Hui Du, Minxuan Zhong, Jiashi Guo, Yao Xie, Yang Xiang, Shengwang Wu, Yiling Yuan, Xinru Yin, Jingyuan Wan, Ke Li
Summary: Protectin D1 (PTD1) improves hepatic steatosis, inflammation and fibrosis in a NASH mouse model by inhibiting the activation of TLR4 downstream signaling pathway, possibly through upregulation of IRAK-M expression, suggesting a potential new treatment for NASH.
FREE RADICAL BIOLOGY AND MEDICINE
(2024)
