Article
Multidisciplinary Sciences
Yuxun Zhang, Eric Goetzman
Summary: Mitochondrial trifunctional protein (TFP) plays a crucial role in chain-shortening long-chain fatty acids within the mitochondria. Despite being heavily modified by acetyllysine and succinyllysine post-translational modifications, the functional significance of these modifications on TFP remains unclear. Research suggests that TFP in the membrane-bound state may be protected from lysine acylation, which could impact its enzymatic activity.
Article
Biochemistry & Molecular Biology
Ravi R. Sonani, Artur Blat, Grzegorz Dubin
Summary: This study solved the crystal structures of human ACOX1a, revealing its homodimeric form and the binding of two FAD molecules at the active site. It also found that the substrate binding cleft of ACOX1a is wider compared to other fatty acid oxidation enzymes. Furthermore, the study analyzed the impact of mutations causing dysfunctionality of ACOX1a on its structure and function.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Genetics & Heredity
Barbara J. Henriques, Rikke Katrine Jentoft Olsen, Claudio M. Gomes, Peter Bross
Summary: Electron transfer flavoprotein (ETF) is an enzyme essential in cellular metabolism, transferring electrons from various enzymes to the respiratory chain to provide reducing power for cells. ETF relays electrons to the respiratory chain by direct transfer between enzyme-bound flavins, promoting electron transport.
Article
Immunology
Abbe N. Vallejo, Henry J. Mroczkowski, Joshua J. Michel, Michael Woolford, Harry C. Blair, Patricia Griffin, Elizabeth McCracken, Stephanie J. Mihalik, Miguel Reyes-Mugica, Jerry Vockley
Summary: The study found that patients with VLCADD exhibit systemic inflammatory responses during symptomatic and asymptomatic periods, with an abundance of immune cells expressing high levels of inflammatory mediators. Patients with recurrent hospitalisations showed sustained high levels of plasma cytokines and higher intracellular stores of inflammatory molecules in monocytes.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Luke T. Izzo, Sophie Trefely, Christina Demetriadou, Jack M. Drummond, Takuya Mizukami, Nina Kuprasertkul, Aimee T. Farria, Phuong T. T. Nguyen, Nivitha Murali, Lauren Reich, Daniel S. Kantner, Joshua Shaffer, Hayley Affronti, Alessandro Carrer, Andrew Andrews, Brian C. Capell, Nathaniel W. Snyder, Kathryn E. Wellen
Summary: The metabolite acetyl-CoA is essential for lipid synthesis and histone acetylation. Citrate and acetate are the primary precursors for nuclear-cytoplasmic acetyl-CoA. This study shows that glucose and fatty acids can contribute to acetyl-CoA pools and histone acetylation, and acetylcarnitine can transport two-carbon units from mitochondria to the cytosol. Glucose can also support fatty acid synthesis in the absence of ACLY, through a carnitine responsive and carnitine acetyltransferase-dependent mechanism.
Article
Biochemistry & Molecular Biology
Rasmus Stenlid, Hannes Manell, Rikard Seth, Sara Y. Cerenius, Azazul Chowdhury, Camilla Roa Cortes, Isabelle Nyqvist, Thomas Lundqvist, Maria Halldin, Peter Bergsten
Summary: This study found that patients with VLCAD and MCAD have significantly lower plasma glucagon concentrations compared to patients with CUD, while the concentrations in the CUD group were similar to normative data, suggesting that glucagon secretion may be impaired in patients with VLCAD or MCAD.
Editorial Material
Clinical Neurology
Brandon B. Holmes, Jeffrey B. Russ, Yvonne W. Wu, Renata C. Gallagher, Dawn Gano
Summary: The newborn male infant was born prematurely at 36 weeks, with low birth weight, but he behaved normally and breastfed well in the first 40 hours of life.
Article
Medical Laboratory Technology
Salim Ahmed Al-Busaidi, Jawaher Al Al Nou'mani, Zubaida Al-Falahi, Rajaa Al-Farsi, Suneel Kumar, Fathiya Al-Murshedi, Kathiya Awlad-Thani, Ayda Al Nabhani, Abdullah M. Al Alawi
Summary: A 14-year-old boy diagnosed with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) also developed type 1 diabetes mellitus (DM1). Managing this patient is challenging due to potentially paradoxical life-threatening complications of the two diseases.
CLINICAL BIOCHEMISTRY
(2023)
Article
Nutrition & Dietetics
Siti Nurjanah, Albert Gerding, Marcel A. Vieira-Lara, Bernard Evers, Miriam Langelaar-Makkinje, Ute Spiekerkoetter, Barbara M. Bakker, Sara Tucci
Summary: Defects in mitochondrial fatty acid beta-oxidation impair energy homeostasis. Very-long-chain acyl-CoA dehydrogenase deficiency is the most common mitochondrial FAO disorder, causing hypoglycemia. Triheptanoin, a dietary treatment, can be metabolized into precursors for gluconeogenesis. Studying the role of gluconeogenesis in long-chain mitochondrial FAO defects, it was found that heptanoate effectively increased glucose production.
Article
Peripheral Vascular Disease
Xiaoyi Zhong, Zhonghong Li, Qingping Xu, Huan Peng, Yongshao Su, Kang Le, Zhaohui Shu, Yingqin Liao, Zhichao Ma, Xuediao Pan, Suowen Xu, Sigui Zhou
Summary: This study investigated the possible role of short-chain acyl-CoA dehydrogenase (SCAD) in hypertension associated vascular remodelling. The expression of SCAD decreased with age and aerobic exercise training increased its expression and decreased vascular remodelling. SCAD expression was also decreased in tBHP-induced endothelial cell apoptosis models and hypertensive patients' aortas. SCAD acts as a negative regulator of vascular remodelling and may be a potential therapeutic target.
JOURNAL OF HYPERTENSION
(2023)
Review
Biochemistry & Molecular Biology
Sofia R. Brandao, Rita Ferreira, Hugo Rocha
Summary: Mitochondria play a crucial role in regulating cell homeostasis, with signaling pathways in mitochondria influencing the phenotype of diseases like FAOD. Specific molecular mechanisms may contribute to the pathogenesis of MADD.
ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY
(2021)
Article
Pediatrics
Tracy L. McGregor, Susan A. Berry, Katrina M. Dipple, Rizwan Hamid
Summary: Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) is a fatty acid oxidation disorder where patients cannot break down fats for energy. Pediatricians should provide acute clinical care for patients with MCADD and work with primary metabolic physicians to prevent adverse outcomes for children.
Article
Biochemistry & Molecular Biology
Dhanendra Tomar, Manfred Thomas, Joanne F. Garbincius, Devin W. Kolmetzky, Oniel Salik, Pooja Jadiya, Suresh K. Joseph, April C. Carpenter, Gyorgy Hajnoczky, John W. Elrod
Summary: MICU1 is a Ca2+-binding protein that regulates mitochondrial Ca2+ uptake and membrane dynamics independently of matrix Ca2+ content. MICU1 interacts with MICOS components MIC60 and CHCHD2 to form the MICOS complex and is essential for proper mitochondrial architecture and cell death signaling. This system allows distinct Ca2+ signaling in the mitochondrial matrix and intermembrane space to modulate cellular energetics and cell death in a coordinated manner.
Article
Endocrinology & Metabolism
Xue-Jun Zhao, AI-Walid Mohsen, Stephanie Mihalik, Keaton Solo, Ermal Aliu, Huifang Shi, Shakuntala Basu, Catherine Kochersperger, Clinton Van't Land, Anuradha Karunanidhi, Kimberly A. Coughlan, Summar Siddiqui, Lisa M. Rice, Shawn Hillier, Eleonora Guadagnin, Paloma H. Giangrande, Paolo G. V. Martini, Jerry Vockley
Summary: Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a genetic disease affecting the heart, liver, and skeletal muscle. Treatment using synthetic human VLCAD mRNA and lipid nanoparticle encapsulated hVLCAD mRNA (LNP-VLCAD) can generate functional VLCAD enzyme in patient cells and improve the metabolic effects of the deficiency.
MOLECULAR GENETICS AND METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Ines Tawfik, Benjamin Gottschalk, Angelo Jarc, Doruntina Bresilla, Rene Rost, Barbara Obermayer-Pietsch, Wolfgang F. Graier, Corina T. Madreiter-Sokolowski
Summary: Thyroid hormones regulate mitochondrial Ca2+ uptake, leading to increased energy metabolism and reactive oxygen species production.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Review
Cell Biology
Mateus Grings, Moacir Wajner, Guilhian Leipnitz
Summary: Ethylmalonic encephalopathy is a severe intoxication disorder caused by mutations in the ETHE1 gene. Disruption of mitochondrial and redox homeostasis, as well as oxidative stress, are important pathomechanisms in tissue damage. Current treatment does not effectively prevent encephalopathy.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Annelise Francisco, Tiago Rezende Figueira, Roger Frigerio Castilho
Summary: Proton-translocating NAD(P)(+) transhydrogenase, known as NNT, plays a crucial role in mitochondrial function and antioxidant pathways. Dysfunctions in NNT have been linked to various metabolic pathways and disease phenotypes, making it a potential target for new therapeutic strategies. Further research is needed to fully understand the role of NNT in physiological and pathological conditions.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Biology
Marina R. Sartori, Claudia D. C. Navarro, Roger F. Castilho, Anibal E. Vercesi
Summary: This study found that the retention capacity of tortoise liver mitochondria for Ca2+ is significantly higher than that of rats, which may be related to the limitations of ANT and cyclophilin D in tortoises. In addition, the rates of H2O2 release and glutathione redox status are similar between tortoises and rats.
JOURNAL OF EXPERIMENTAL BIOLOGY
(2022)
Article
Neurosciences
Leticia Barbieri Caus, Mayara Vendramin Pasquetti, Bianca Seminotti, Michael Woontner, Moacir Wajner, Maria Elisa Calcagnotto
Summary: This study investigated the impact of quinolinic acid on the neurological features of GA-I, finding that Gcdh(-/-)-Lys mice showed increased susceptibility to quinolinic acid-induced seizures and enduring alterations in brain oscillation patterns.
JOURNAL OF NEUROSCIENCE RESEARCH
(2022)
Review
Endocrinology & Metabolism
Josi Vidart, Paula Jaskulski, Ana Laura Kunzler, Rafael Aguiar Marschner, Andre Ferreira de Azeredo da Silva, Simone Magagnin Wajner
Summary: We conducted a systematic review and meta-analysis to determine the prevalence and prognostic role of non-thyroidal illness syndrome (NTIS) in critically ill patients. The results suggest that decreased thyroid function may be associated with a worse outcome in critically ill patients.
ENDOCRINE CONNECTIONS
(2022)
Article
Multidisciplinary Sciences
Juliana S. Ruas, Edilene S. Siqueira-Santos, Claudia D. C. Navarro, Roger F. Castilho
Summary: Mitochondrial oxygen consumption measurement is valuable for evaluating mitochondrial function, but adding oligomycin may lead to underestimation. This study presents an improved protocol to overcome this issue and is applicable to various cell lines.
Article
Biochemistry & Molecular Biology
Thamires Siqueira de Oliveira, Marilia Kimie Shimabukuro, Victoria Regina Siqueira Monteiro, Cherley Borba Vieira Andrade, Anita Boelen, Simone Magagnin Wajner, Ana Luiza Maia, Tania Maria Ortiga-Carvalho, Flavia Fonseca Bloise
Summary: This study investigates the impact of inflammation on thyroid hormone signaling during myogenesis. The results show that inflammation can reduce the myogenic stimulus and alter intracellular metabolism of thyroid hormones. However, late differentiation is not affected by the inflammatory milieu.
Article
Neurosciences
Rafael Teixeira Ribeiro, Andrey Vinicios Soares Carvalho, Rafael Palavro, Luz Elena Duran-Carabali, Angela Beatris Zemniacak, Alexandre Umpierrez Amaral, Carlos Alexandre Netto, Moacir Wajner
Summary: L-2-Hydroxyglutaric aciduria (L-2-HGA) is a genetic disorder characterized by deficient activity of l-2-hydroxyglutarate dehydrogenase, leading to the accumulation of l-2-hydroxyglutaric acid (L-2-HG) in the brain and biological fluids. This results in neurological symptoms and brain abnormalities, particularly in the cerebral cortex, basal ganglia, and cerebellum. A study using neonatal rats showed that intracerebroventricular injection of L-2-HG caused oxidative stress in the cerebellum, leading to neuronal loss, demyelination, astrocyte reactivity, and increased inflammatory response in the cerebral cortex and striatum. L-2-HG administration also resulted in a delay in neuromotor development and cognitive deficits in adult animals, which were prevented by the antioxidant melatonin.
NEUROTOXICITY RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Josi Vidart, Luiza Axelrud, Andre Cardoso Braun, Rafael Aguiar Marschner, Simone Magagnin Wajner
Summary: Low T3 syndrome is common in patients with sepsis. The expression of DIO3 in white cells explains the reduction in T3 levels, and low T3 levels independently predict mortality and evolution to chronic critical illness in patients with sepsis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Rafael Aguiar Marschner, Ana Cristina Roginski, Rafael Teixeira Ribeiro, Larisse Longo, Mario Reis Alvares-da-Silva, Simone Magagnin Wajner
Summary: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a global public health problem, but effective treatments are limited due to lack of mechanistic knowledge. This study evaluated the role of type 3 deiodinase (D3) in the progression of MAFLD using an animal model. The findings suggest that induced D3 decreases T3 availability and hepatic mitochondrial capacity, leading to alterations in Krebs cycle enzymes and endoplasmic reticulum stress.
Article
Cell Biology
Ellen A. A. Silva, Ana P. P. Dalla Costa, Juliana S. S. Ruas, Edilene S. S. Siqueira-Santos, Annelise Francisco, Roger F. F. Castilho
Summary: Understanding the oxidative metabolism of proliferating astrocytes is necessary for understanding their role in the development of the nervous system and neurodegenerative disorders. This study assessed the impact of mitochondrial oxidative metabolism on astrocyte survival and proliferation by inhibiting mitochondrial respiration and ATP synthesis in primary astrocytes from neonatal mice. The results showed that astrocytes can sustainably proliferate with glycolytic metabolism and do not require electron flux through respiratory complex I or oxidative phosphorylation for growth and survival.
Article
Biochemistry & Molecular Biology
Leonardo Luis Artico, Juliana Silveira Ruas, Jose Ricardo Teixeira Junior, Natacha Azussa Migita, Gustavo Seguchi, Xinghua Shi, Silvia Regina Brandalise, Roger Frigerio Castilho, Jose Andres Yunes
Summary: IGFBP7 promotes the permanence of IGF1R on the cell surface, prolonging Akt activation in the PI3K-Akt axis, which contributes to energy metabolism and glycolytic metabolism enhancement in BCP-ALL. Neutralizing IGFBP7 or inhibiting the PI3K-Akt pathway can restore the physiological levels of GLUT1 on the cell surface. This metabolic effect provides a mechanistic explanation for the negative impact of IGFBP7 knockdown or antibody neutralization on B cells in vitro and in vivo, highlighting its potential as a therapeutic target.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Vanessa Trindade Bortoluzzi, Rafael Teixeira Ribeiro, Angela Beatris Zemniacak, Samela de Azevedo Cunha, Joern Oliver Sass, Roger Frigerio Castilho, Alexandre Umpierrez Amaral, Moacir Wajner
Summary: Research suggests that the accumulation of N-acetylglutamate (NAG) and N-acetylmethionine (NAM) in ACY1 deficiency may have toxic effects on the brain, disrupting mitochondrial functions and contributing to neuropathology.
NEUROCHEMISTRY INTERNATIONAL
(2023)
Article
Thermodynamics
Marina Rincon Sartori, J. Lerchner, R. F. Castilho, P. O. Volpe, F. Mertens, A. E. Vercesi
Summary: Ca2+ signaling in trypanosomatids plays an important role in energy metabolism regulation, with Ca2+ concentration being finely regulated within cellular compartments. Research shows that heat is generated during Ca2+ uptake by mitochondria and acidocalcisomes, with mitochondria exhibiting minimal heat dissipation and ATPase pumps in acidocalcisomes contributing significantly to the heat generated.
JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY
(2022)