Article
Biochemistry & Molecular Biology
Chiara Diquigiovanni, Nicola Rizzardi, Antje Kampmeier, Irene Liparulo, Francesca Bianco, Bianca De Nicolo, Erica Cataldi-Stagetti, Elisabetta Cuna, Giulia Severi, Marco Seri, Miriam Bertrand, Tobias B. Haack, Adela Della Marina, Frederik Braun, Romana Fato, Alma Kuechler, Christian Bergamini, Elena Bonora
Summary: Pathogenic variants in SPART cause Troyer syndrome characterized by spasticity, weakness, short stature, cognitive impairment, and severe mitochondrial dysfunction. This study identified a role of Spartin in nuclear-encoded mitochondrial proteins. Fibroblasts derived from a patient with SPART missense variants showed mitochondrial abnormalities, reduced respiration, increased reactive oxygen species, and altered calcium levels. Impaired mitochondrial import was observed in these fibroblasts and in a cell model with a SPART loss-of-function mutation, resulting in decreased levels of different proteins, including key enzymes involved in CoQ synthesis. CoQ supplementation restored ATP levels, suggesting it as a potential therapeutic approach for patients with SPART mutations.
Article
Biochemistry & Molecular Biology
Joao Paulo Cavalcanti-de-Albuquerque, Eduardo de-Souza-Ferreira, Denise Pires de Carvalho, Antonio Galina
Summary: The interaction between hexokinase (HK) and the GABA shunt plays a role in controlling mitochondrial metabolism in the cortex and hypothalamus. The GABA shunt stimulates mitochondrial oxygen consumption and H2O2 production in the hypothalamus, while increasing the coupling of HK to OXPHOS activity.
NEUROCHEMICAL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Takaya Ishihara, Reiko Ban-Ishihara, Azusa Ota, Naotada Ishihara
Summary: Mitochondria have their own DNA, called mtDNA, which encodes respiratory subunits. Under live imaging, mitochondrial nucleoids actively move and change morphology with mitochondrial membrane fission. The AAA-ATPase protein ATAD3A, anchored to the inner membrane, mediates nucleoid dynamics through ATP hydrolysis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Editorial Material
Cell Biology
Christopher A. Denaro, Yara Haloush, Samuel Y. Hsiao, John J. Orgera, Teresa Osorio, Lindsey M. Riggs, Joshua W. Sassaman, Sarah A. Williams, Anthony R. Monte Carlo, Renata T. Da Costa, Andrey Grigoriev, Maria E. Solesio
Summary: There is a significant lack of knowledge regarding the molecular mechanisms and long-term consequences of SARS-CoV-2 infection in humans, especially its effects on the central nervous system and neurodegenerative disorders.
Article
Biochemistry & Molecular Biology
Parameswaran Gangadharan Sreekumar, Feng Su, Christine Spee, Elise Hong, Ravikiran Komirisetty, Eduardo Araujo, Steven Nusinowitz, Srinivasa Reddy, Ram Kannan
Summary: Oxidative stress plays a crucial role in the development of AMD, and PON2 has been found to have a beneficial role in preserving retinal function and protecting against mitochondrial dysfunction.
Article
Neurosciences
Ozan Baytas, Julie A. Kauer, Eric M. Morrow
Summary: This study reveals a novel mechanism of degeneration of locus coeruleus (LC) neurons caused by loss of the mitochondrial enzyme GPT2. The loss of LC neurons in Gpt2-null mice is found to be the earliest during development compared to other genetic animal models, providing important insights into the metabolic vulnerability of LC.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Cell Biology
Patricia Sinclair, Ancha Baranova, Nadine Kabbani
Summary: This study revealed that Aβ(42) disrupts proteome responses for signaling, bioenergetics, and morphology in mitochondria. These findings highlight the specific components of the mitochondrial response during Aβ(42) neurotoxicity and suggest several new biomarkers for detection and surveillance of amyloid disease.
Article
Environmental Sciences
Lingyue Zou, Binjing Li, Lilin Xiong, Yan Wang, Wenjing Xie, Xiaoquan Huang, Ying Liang, Tingting Wei, Na Liu, Xiaoru Chang, Changcun Bai, Tianshu Wu, Yuying Xue, Ting Zhang, Meng Tang
Summary: Studies have shown that exposure to PM2.5 can lead to cardiac hypertrophy and mitochondrial dysfunction, which can trigger cardiovascular diseases.
ENVIRONMENTAL POLLUTION
(2022)
Article
Biochemistry & Molecular Biology
Peina Wang, Yanmei Cui, Yuanyuan Liu, Zhongda Li, Huiyuan Bai, Yashuo Zhao, Yan-Zhong Chang
Summary: Oxidative stress and deficient bioenergetics play important roles in cerebral ischemia reperfusion injury. Mitochondrial ferritin (FtMt) protects neuronal cells from oxidative damage and apoptosis under stress conditions. The present study demonstrates that FtMt deficiency exacerbates neuronal apoptosis while FtMt overexpression inhibits apoptosis and ER stress response. FtMt also improves mitochondrial function and regulates glucose metabolism via the pentose-phosphate pathway, thus preventing ROS overproduction and preserving energy metabolism. These findings highlight the significance of FtMt in cerebral ischemia reperfusion injury.
Article
Biochemistry & Molecular Biology
Paul J. Kamitsuka, Marwan M. Ghanem, Rania Ziar, Sarah E. McDonald, Morgan G. Thomas, Gunnar F. Kwakye
Summary: Exposure to cadmium (Cd), a heavy metal, can induce neurotoxicity and cell death. In this study, the researchers found that mutant huntingtin protein (mHTT) cells are more susceptible to acute Cd-induced cell death compared to wild-type (WT) cells. They also discovered that mHTT and acute Cd exposure synergistically impair mitochondrial bioenergetics and protein degradation mechanisms, leading to cell death. Furthermore, Cd exposure promotes neurodegeneration in Huntington's disease (HD) striatal cells by impairing autophagy and altering protein degradation pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Ryan J. J. Mailloux, Cathryn Grayson, Olivia Koufos
Summary: Protein S-glutathionylation has been proposed as a regulator of cell metabolism for four decades. This redox-sensitive covalent modification serves as a cell-wide signaling platform and plays a key role in embryonic development and regulation of physiological functions. It functions as a feedback loop for inhibiting mitochondrial hydrogen peroxide (H2O2) production and desensitizing mitochondrial redox signals.
Article
Neurosciences
Eleonora Napoli, Amanda Flores, Yasmeen Mansuri, Randi J. Hagerman, Cecilia Giulivi
Summary: CGG expansions in the 5'-untranslated region of the FMR1 gene increase the risk of FXTAS, and sulforaphane has shown beneficial effects on pathways related to brain function in fibroblasts from FXTAS-affected subjects, paving the way for potential clinical studies in treating FXTAS.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Environmental Sciences
Nissaf Aoiadni, Hajer Jdidi, Abdelfattah El Feki, Hamadi Fetoui, Fatma Ghorbel Koubaa
Summary: The present study evaluated the potential anti-inflammatory and nephroprotective effects of ethyl acetate fraction extracted from Fumaria officinalis (EAF) against permethrin (PER). In vitro results showed that EAF could inhibit protein denaturation and heat-induced hemolysis. In vivo, PER treatment induced oxidative stress and kidney damage, while co-treatment with EAF improved antioxidant status and mitochondrial bioenergetics.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2022)
Article
Neurosciences
Chen Shen, Cong Chen, Tong Wang, Tong-Yao Gao, Min Zeng, Yun-Bi Lu, Wei-Ping Zhang
Summary: Nicotinamide phosphoribosyltransferase (NAMPT) is a key enzyme in the salvaging synthesis pathway of nicotinamide adenine dinucleotide (NAD). Depletion of NAMPT can lead to cognitive deficiency in hippocampus neurons and increase the risk of neurodegeneration due to mitochondrial dysfunction.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Geriatrics & Gerontology
Wagner S. Dantas, Elizabeth R. M. Zunica, Elizabeth C. Heintz, Bolormaa Vandanmagsar, Z. Elizabeth Floyd, Yongmei Yu, Hisashi Fujioka, Charles L. Hoppel, Kathryn P. Belmont, Christopher L. Axelrod, John P. Kirwan
Summary: Mitochondrial uncoupling with BAM15 reduces body weight by increasing energy expenditure, improves muscle mass, strength, and activity while reducing inflammation, limiting ER stress, apoptosis, and muscle protein degradation in a mouse model of sarcopenic obesity. These findings suggest that BAM15 may protect against age-related decline in muscle mass and function through bioenergetic adaptations.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2022)
Article
Oncology
Yi Hu, Chun Yang, Tania Amorim, Mohsin Maqbool, Jenny Lin, Chen Li, Chuanfeng Fang, Li Xue, Ariel Kwart, Hua Fang, Mei Yin, Allison J. Janocha, Daisuke Tsuchimoto, Yusaku Nakabeppu, Xiaofeng Jiang, Alex Mejia-Garcia, Faiz Anwer, Jack Khouri, Xin Qi, Qing Y. Zheng, Jennifer S. Yu, Shan Yan, Thomas LaFramboise, Kenneth C. Anderson, Leal C. Herlitz, Nikhil C. Munshi, Jianhong Lin, Jianjun Zhao
Summary: This study identified APE2 as a critical molecule upregulated in the kidney following cisplatin treatment, leading to MYH9 dysfunction in mitochondria and potential development of AKI. Knockout of APE2 attenuated cisplatin-induced kidney injury, suggesting a novel target for prophylactic treatment of AKI.
Article
Biochemistry & Molecular Biology
Di Hu, Zunren Liu, Xin Qi
Summary: This study found that activation of UPRmt can reduce mitochondrial reactive oxygen species (ROS) production and improve cell survival in MPP+-treated cells. Overexpression of specific transcription factor 5 can protect cells from MPP+-induced oxidative stress and cell death.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Mukesh Mahajan, Nikhil Bharambe, Yutong Shang, Bin Lu, Abhishek Mandal, Pooja Madan Mohan, Rihua Wang, Jennifer C. Boatz, Juan Manuel Martinez Galvez, Anna Shnyrova, Xin Qi, Matthias Buck, Patrick C. A. van der Wel, Rajesh Ramachandran
Summary: The study elucidated the interaction mechanism between Drp1 and mitochondrial outer membrane cardiolipin, which triggers mitochondrial hyperfragmentation under stress conditions. Mutations in the CBM weakened this interaction, impairing Drp1-dependent fission under stress and inducing the formation of donut-shaped mitochondria.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Clinical Neurology
Chunlei Zheng, Nathanael R. Fillmore, Jaime Ramos-Cejudo, Mary Brophy, Ricardo Osorio, Mark E. Gurney, Wei Qiao Qiu, Rhoda Au, George Perry, Maureen Dubreuil, Shu G. Chen, Xin Qi, Pamela B. Davis, Nhan Do, Rong Xu
Summary: The long-term use of TNF inhibitors is associated with a lower risk of dementia/AD among US veterans with RA, as shown in a retrospective cohort study conducted over a 20-year period.
ALZHEIMERS & DEMENTIA
(2022)
Article
Biochemistry & Molecular Biology
Chang Yoon Doh, Nikhil Bharambe, Joshua B. Holmes, Katherine L. Dominic, Caitlin E. Swanberg, Ranganath Mamidi, Yinghua Chen, Smarajit Bandyopadhyay, Rajesh Ramachandran, Julian E. Stelzer
Summary: The flexible interdomain linker and cardiac-isoform specific loop in the central C4 and C5 domains of cMyBPC play important roles in its functional regulation. These regions modulate the secondary structure and thermal stability of C4C5, and can adopt a completely bent or latched conformation, as demonstrated through extended molecular dynamics simulations and principle component analyses.The hinge-and-latch mechanism proposed in this study suggests that the linker and loop regions participate in dynamic modulation of cMyBPC's motion and global conformation.
JOURNAL OF STRUCTURAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Yuanyuan Zhao, Di Hu, Rihua Wang, Xiaoyan Sun, Philip Ropelewski, Zita Hubler, Kathleen Lundberg, Quanqiu Wang, Drew J. Adams, Rong Xu, Xin Qi
Summary: This study identifies ATAD3A oligomerization as a key mechanism causing impaired cholesterol metabolism and neuropathology in AD models. Suppressing ATAD3A oligomerization can reduce pathological changes and cognitive deficits in AD.
NATURE COMMUNICATIONS
(2022)
Review
Neurosciences
Aya Jishi, Xin Qi
Summary: Increasing evidence suggests that mitochondrial dysfunction plays a key role in the development and progression of various neurodegenerative diseases. The diverse functions of mitochondria require tight regulation of protein import, dynamics, and turnover, which can be affected in several major proteinopathies. Failure of these regulatory mechanisms compromises mitochondrial function and exacerbates pathogenic processes.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Biochemical Research Methods
Filipa Blasco Tavares Pereira Lopes, Daniela Schlatzer, Rihua Wang, Xiaolin Li, Emily Feng, Mehmet Koyuturk, Xin Qi, Mark R. Chance
Summary: Mouse models of Alzheimer's disease can be used to study the progression of the disease and identify factors that drive AD-related pathways. This study used proteomics to analyze the hippocampus tissue of mice at different time points and with different genetic backgrounds and sexes. The results showed that 5XFAD mice exhibited increases in known AD biomarkers and also identified new proteins associated with AD pathology. Pathway analysis revealed sex-linked differences in the 5XFAD model related to amyloid fibril formation, wound healing, lysosome biogenesis, and DNA damage.
MOLECULAR & CELLULAR PROTEOMICS
(2022)
Letter
Multidisciplinary Sciences
Isabel Perez-Jover, Pooja Madan Mohan, Rajesh Ramachandran, Anna Shnyrova
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Pharmacology & Pharmacy
Shuai Wang, Xin Qi
Summary: Astaxanthin, a natural xanthophyll carotenoid, shows neuroprotective effects by alleviating oxidative stress, reducing the production of neuroinflammatory factors, and maintaining the integrity of the blood-brain barrier. It modulates neuroinflammation through mechanisms such as scavenging radicals, activating antioxidant systems, and suppressing inflammatory pathways. Further research is needed to fully understand its potential in treating neurological diseases.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Clinical Neurology
Yutong Shang, Xiaoyan Sun, Xiaoqin Chen, Quanqiu Wang, Evan J. Wang, Emiko Miller, Rong Xu, Andrew A. Pieper, Xin Qi
Summary: This study reveals that CHCHD6 mechanistically connects APP processing and mitochondrial dysfunction in Alzheimer's disease through a circular feedback loop. Reduced CHCHD6 enhances APP accumulation on mitochondria-associated ER membranes, accelerates APP processing, and induces mitochondrial dysfunction and neuronal cholesterol accumulation, promoting amyloid pathology in Alzheimer's disease.
ACTA NEUROPATHOLOGICA
(2022)
Article
Neurosciences
Shivangi Gupta, Poonam Sharma, Mansi Chaudhary, Sharanya Premraj, Simran Kaur, Vijithkumar Vijayan, Manas Geeta Arun, Nagaraj Guru Prasad, Rajesh Ramachandran
Summary: Unlike mammals, zebrafish have the ability to regenerate damaged retina. This study reveals the importance of Phosphatase and tensin homolog (Pten) in zebrafish retina regeneration and identifies multiple signaling pathways involved in Pten's regulation of retinal cell proliferation.
Article
Cell Biology
Kayla K. Troutman, Natalia V. Varlakhanova, Bryan A. Tornabene, Rajesh Ramachandran, Marijn G. J. Ford
Summary: This study investigates the regulatory mechanisms of Pib2 on TORC1. It demonstrates that the N-terminal region of Pib2 has an inhibitory function on TORC1, while the C-terminal region is critical for TORC1 reactivation. In addition, the FYVE domain of Pib2 plays a role in vacuolar localization but is not necessary for TORC1 recovery.
JOURNAL OF CELL SCIENCE
(2022)
Review
Cell Biology
Cassandra Barone, Xin Qi
Summary: Motor Neuron Diseases (MND) are neurological disorders characterized by a loss of motor neurons resulting in decreased physical capabilities. Current research aims to hinder disease progression by understanding the causes of motor neuron death, particularly focusing on metabolic malfunction as a potential therapeutic target. This review highlights the importance of a cohesive system involving both neurons and skeletal muscle tissue and proposes potential metabolic deficits as targets for future intervention.
Article
Physiology
Jason A. Mears, Rajesh Ramachandran
Summary: This review provides an overview of the interactions between the master regulator of mitochondrial division, Drp1, and the cytoskeletal elements, highlighting the roles of the cytoskeleton in modulating and mediating mitochondrial division, as well as its potential role as a diffusion barrier.
CURRENT OPINION IN PHYSIOLOGY
(2022)