Article
Environmental Sciences
Lu Lu, Jing-Bo Liu, Jin-Qiu Wang, Cai-Yu Lian, Zhen-Yong Wang, Lin Wang
Summary: Glyphosate (GLY) induces mitochondrial dysfunction and mitochondrial reactive oxygen species (mtROS) overproduction, leading to the activation of parkin-dependent mitophagy and ultimately inhibiting testosterone synthesis.
ENVIRONMENTAL POLLUTION
(2022)
Article
Biochemistry & Molecular Biology
Xuan Sun, Yifei Wang, Qingyang Mai, Yixuan Fan, Qunhao Huang, Yingli Du, Hai Huang, El-Samahy Ma, Feng Wang, Guomin Zhang
Summary: The study reveals that Neuromedin S (NMS) and its receptors are mainly expressed in Leydig cells (LCs) of goat testes, with the highest expression detected at age three months. NMS addition significantly enhances testosterone secretion and cell proliferation in vitro cultured goat LCs by modulating mitochondrial morphology, function, and autophagy. These findings provide a novel view of the regulatory mechanisms involved in male sexual maturation.
Article
Environmental Sciences
Zorimar Rivera-Nunez, Megan Hansel, Camila Capurro, Danielle Kozlosky, Christina Wang, Cathleen L. Doherty, Brian Buckley, Pamela Ohman-Strickland, Richard K. Miller, Thomas G. O'Connor, Lauren M. Aleksunes, Emily S. Barrett
Summary: This study found that cadmium exposure during pregnancy may lead to lower testosterone levels in pregnant women, while estrogen levels remain unchanged. This effect may be stronger in pregnancies carrying female fetuses. Further research is needed to understand how alterations in gestational testosterone activity may impact pregnancy and child health.
Article
Reproductive Biology
Jin-Yong Chung, Haolin Chen, Barry Zirkin
Summary: Inhibition or knockout of Sirt1 or Nrf2 resulted in increased ROS and reduced cell testosterone production, and their activation protected or enhanced steroidogenic function, suggesting that Sirt1 and Nrf2 are involved in maintaining the Leydig cell oxidant/antioxidant environment and steroid production.
BIOLOGY OF REPRODUCTION
(2021)
Article
Endocrinology & Metabolism
Xiaoheng Li, Qiqi Zhu, Zina Wen, Kaimin Yuan, Zhijian Su, Yiyan Wang, Ying Zhong, Ren-Shan Ge
Summary: This study demonstrates that luteinizing hormone (LH) and androgens regulate the function of immature Leydig cells in rats through different transcriptional pathways. LH up-regulated the expression of specific genes, while androgens showed opposite effects on certain genes. Ultimately, LH and androgens play distinct roles in the regulation of Leydig cell function.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Philipp Melchinger, Bruna Martins Garcia
Summary: Steroids play important roles in maintaining cellular homeostasis as membrane components and signaling metabolites. Both uptake and synthesis of steroids are crucial for mammalian cells. Dysregulation of steroid levels has profound effects on cellular function and overall health. Mitochondria, primarily located in the endoplasmic reticulum, are essential for cholesterol production and processing of steroid products. Understanding the regulatory roles of mitochondria in steroid synthesis can lead to targeted approaches for controlling steroid levels.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2023)
Article
Obstetrics & Gynecology
Megan C. Hansel, Hannah R. Murphy, Jessica Brunner, Christina Wang, Richard K. Miller, Thomas G. O'Connor, Emily S. Barrett, Zorimar Rivera-Nunez
Summary: The study found that neighborhood stressors were associated with higher levels of maternal testosterone, which may have implications for maternal and child health.
BMC PREGNANCY AND CHILDBIRTH
(2023)
Article
Ophthalmology
Evan D. Bogdan, Whitney L. Stuard, Rossella Titone, Danielle M. Robertson
Summary: The study demonstrates that IGFBP-3 plays a critical role in the corneal epithelium's response to hyperosmolar stress, and supports a new function for IGFBP-3 in regulating cellular metabolism.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Review
Cell Biology
Wenjiao Liu, Ting Gong, Fangxiong Shi, Houqiang Xu, Xiang Chen
Summary: This article explores the signaling mechanisms through which taste receptor factors influence testosterone synthesis in male reproduction and discusses their potential role in regulating male fertility.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Endocrinology & Metabolism
Ying Meng, Loralei L. Thornburg, Kathleen M. Hoeger, Zorimar Rivera- Nunez, Amber Kautz, Adam T. Evans, Christina Wang, Richard K. Miller, Susan W. Groth, Thomas G. O'Connor, Emily S. Barrett
Summary: This study aimed to assess the relationships between early-pregnancy sex steroid hormones and the subsequent development of hyperglycemia during pregnancy, as well as the associations between sex steroid hormone levels and gestational diabetes diagnosis. The results showed that total testosterone, free testosterone, and estrone in early pregnancy were positively associated with glucose levels and gestational diabetes in mid-late pregnancy. These hormones may serve as early predictors of gestational diabetes along with other risk factors.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Medicine, General & Internal
Jeanette Buchhardt, Wieland Kiess, Antje Koerner, Ronald Biemann, Christian Hirsch
Summary: Tooth wear is common in children and adolescents, and it increases with age in both sexes. The higher prevalence and faster increase in male adolescents can be explained by the additional effect of free testosterone.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Endocrinology & Metabolism
Prasanthi P. Koganti, Amy H. Zhao, Vimal Selvaraj
Summary: This study uncovered that murine Leydig cells remain responsive to exogenous cholesterol delivery by lipoproteins in the presence of serum, highlighting the importance of Rho-GTPase signaling pathways in the regulation of steroid biosynthesis. These findings challenge the long-held view of serum interference and underscore the need for exogenous lipoproteins for studying cholesterol trafficking and physiological signaling in vitro. The LH-responsive MA-10(Slip) clones derived in this study present a reformed platform for studying mammalian steroidogenesis.
JOURNAL OF ENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Tessa M. Cacciottolo, Elana Henning, Julia M. Keogh, Pierre Bel Lassen, Katherine Lawler, Rebecca Bounds, Rachel Ahmed, Aliki Perdikari, Edson Mendes de Oliveira, Miriam Smith, Edmund M. Godfrey, Elspeth Johnson, Leanne Hodson, Karine Clement, Agatha A. van der Klaauw, I. Sadaf Farooqi
Summary: SRC-1 variant carriers exhibit hyperphagia in childhood, severe obesity, and clinical features of partial hormone resistance. The presence of adipose tissue fibrosis and hepatic fibrosis in young patients suggests that close monitoring for the early development of obesity-associated metabolic complications is warranted.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Kang Nian Yap, Hoi Shan Wong, Chidambaram Ramanathan, Cristina Aurora Rodriguez-Wagner, Michael D. Roberts, David A. Freeman, Rochelle Buffenstein, Yufeng Zhang
Summary: Naked mole-rats and Damaraland mole-rats, with their small body size, exhibit extraordinary longevity, high tolerance to hypoxia and oxidative stress, and high reproductive output. Their unique bioenergetic properties, including low basal metabolic rates, a high dependence on glycolysis for ATP production, and low proton conductance across the mitochondrial inner membrane, may be an evolutionary adaptation to variable oxygen environments and a molecular mechanism underlying their extremely long lifespans.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2022)
Article
Oncology
Alexander Pfab, Sergey Belikov, Michaela Keuper, Martin Jastroch, Mattias Mannervik
Summary: This study found that the neurotoxin symbolscript can trigger cell death of dopamine neurons, leading to Parkinson's disease symptoms. Additionally, the neurotoxin directly affects mitochondrial function and transcription, resulting in reduced ATP production. These findings reveal the direct effects of symbolscript on cellular processes, while other gene expression or epigenetic changes are secondary effects reflecting cellular adaptation.
EXPERIMENTAL CELL RESEARCH
(2023)
Review
Andrology
Vassilios Papadopoulos, Lu Li, Mary Samplaski
Summary: Recent epidemiological data suggest a gender predisposition to COVID-19, with older men being most severely affected and at higher risk of death. Low testosterone levels may exacerbate the severity of COVID-19 infection in elderly men, while normal levels might offer protection. Additional testing for gonadal function and testosterone treatment may be warranted in elderly males to reduce mortality related to COVID-19.
Article
Biochemistry & Molecular Biology
Jinjiang Fan, Vassilios Papadopoulos
Summary: Deletion of the TSPO gene in MA-10 cells results in reduced mitochondrial membrane potential and significant changes in nuclear gene expression. This is likely due to dysregulation of several signaling pathways, including those involved in regulating membrane potential, calcium signaling, extracellular matrix, and phagocytosis. The compensatory response to loss of TSPO involves changes in expression of transcription factors, such as key members of the NF-kappa B pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
A. Roichman, S. Elhanati, M. A. Aon, I Abramovich, A. Di Francesco, Y. Shahar, M. Y. Avivi, M. Shurgi, A. Rubinstein, Y. Wiesner, A. Shuchami, Z. Petrover, I Lebenthal-Loinger, O. Yaron, A. Lyashkov, C. Ubaida-Mohien, Y. Kanfi, B. Lerrer, P. J. Fernandez-Marcos, M. Serrano, E. Gottlieb, R. de Cabo, H. Y. Cohen
Summary: The study demonstrates that overexpression of SIRT6 extends lifespan in mice and optimizes energy homeostasis in old age, delaying frailty and preserving healthy aging. Aged SIRT6-transgenic mice maintain hepatic glucose output and glucose homeostasis through improved utilization of two major gluconeogenic precursors, lactate, and glycerol.
NATURE COMMUNICATIONS
(2021)
Article
Cardiac & Cardiovascular Systems
Sonia Cortassa, Miguel A. Aon, Magdalena Juhaszova, Evgeny Kobrinsky, Dmitry B. Zorov, Steven J. Sollott
Summary: ATP synthase plays a crucial role in ATP synthesis, and in addition to transporting H+, it also transports K+. Computational modeling has been used to demonstrate the feasibility of this mechanism and explore its implications in bioenergetics.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
Article
Endocrinology & Metabolism
Melanie Galano, Vassilios Papadopoulos
Summary: The steroidogenic acute regulatory protein (STAR) is critical for cholesterol transport into the mitochondria and plays a role in its processing. This study found that deficiency or overexpression of STAR can lead to mitochondrial dysfunction, suggesting the importance of constitutive STAR for proper mitochondrial structure and function.
Review
Biochemistry & Molecular Biology
Melanie Galano, Sathvika Venugopal, Vassilios Papadopoulos
Summary: This review discusses the importance of cholesterol transport proteins and their roles in the trafficking and metabolism of cholesterol and other lipids in cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Andrology
Samuel Garza, Vassilios Papadopoulos
Summary: Reduced serum testosterone has negative effects on men's health and quality of life, and finding alternative treatments to testosterone replacement therapy is desirable. Research on testosterone formation in Leydig cells has identified potential targets for increasing endogenous testosterone biosynthesis. Enhancing steroidogenesis in Leydig cells could be an effective therapeutic approach, however, the development of ligands for steroidogenic proteins may have off-target effects. First-in-class biologics and transplantation of induced human Leydig-like cells offer promising strategies for enhancing endogenous steroid formation in hormone deficient patients.
Article
Biochemistry & Molecular Biology
Samuel Garza, Liting Chen, Melanie Galano, Garett Cheung, Chantal Sottas, Lu Li, Yuchang Li, Barry R. Zirkin, Vassilios Papadopoulos
Summary: This study found that the decline of mitochondrial translocator protein (TSPO) may result in disruptions in mitochondrial function and morphology, and is associated with declining Leydig cell (LC) function and reduced testosterone levels in the blood. Restoring mitochondrial function and promoting steroid formation can be achieved by enhancing mitochondrial fusion. These findings suggest that maintaining or enhancing mitochondrial fusion may be a therapeutic strategy for maintaining testosterone levels during aging.
Article
Biology
Kirill Tarasov, Khalid Chakir, Daniel R. Riordon, Alexey E. Lyashkov, Ismayil Ahmet, Maria Grazia Perino, Allwin Jennifa Silvester, Jing Zhang, Mingyi Wang, Yevgeniya O. Lukyanenko, Jia-Hua Qu, Miguel Calvo-Rubio Barrera, Magdalena Juhaszova, Yelena S. Tarasova, Bruce Ziman, Richard Telljohann, Vikas Kumar, Mark Ranek, John Lammons, Rostislav Bychkov, Rafael de Cabo, Seungho Jun, Gizem Keceli, Ashish Gupta, Dongmei Yang, Miguel A. Aon, Luigi Adamo, Christopher H. Morrell, Walter Otu, Cameron Carroll, Shane Chambers, Nazareno Paolocci, Thanh Huynh, Karel Pacak, Robert Weiss, Loren Field, Steven J. Sollott, Edward G. Lakatta
Summary: This study found that overexpression of AC8 in mice enables them to adapt to an increased cardiac workload and triggers various adaptive changes. Compared to wild type mice, TG(AC8) mice showed increased number of cardiac myocytes, proliferation of non-cardiac myocytes, enhanced protein synthesis, and metabolic pathway shifts.
Article
Cell Biology
Lu Li, Chantal M. Sottas, Hsu-Yu Chen, Yuchang Li, Haoyi Cui, Jason S. Villano, Joseph L. Mankowski, Paula M. Cannon, Vassilios Papadopoulos
Summary: Our study shows that SARS-CoV-2 can enter human Leydig-like cells (hLLCs) through a distinct pathway and alter testosterone production. This finding is significant for understanding the impact of the SARS-CoV-2 virus on the human body and the mechanisms of disease transmission.
Review
Biochemistry & Molecular Biology
Liting Chen, Yuchang Li, Alexander Zambidis, Vassilios Papadopoulos
Summary: Mitochondrial membrane protein ATAD3A is crucial for the maintenance of mitochondrial DNA, structure, and function. Mutations in ATAD3A have been found to disrupt mitochondrial structure, function, and dynamics, leading to severe neurological symptoms and early mortality. This review highlights the importance of ATAD3A in mitochondrial dynamics and its interaction with other mitochondrial/ER proteins. It also discusses the impact of ATAD3A mutations on various mitochondrial functions, including autophagy, mitophagy, mitochondrial morphology, and respiratory chain activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Geriatrics & Gerontology
Michel Bernier, Ignacio Navas Enamorado, Mari Carmen Gomez-Cabrera, Miguel Calvo-Rubio, Jose Antonio Gonzalez-Reyes, Nathan L. Price, Ana Belen Cortes-Rodriguez, Juan Carlos Rodriguez-Aguilera, Sandra Rodriguez-Lopez, Sarah J. Mitchell, Kelsey N. Murt, Krystle Kalafut, Katrina M. Williams, Christopher W. Ward, Joseph P. Stains, Gloria Brea-Calvo, Jose M. Villalba, Sonia Cortassa, Miguel A. Aon, Rafael de Cabo
Summary: This study investigates the effects of different exercise training modalities on skeletal muscle adaptation in adult and old mice. The results show that moderate intensity continuous training leads to improvements in body composition, blood glucose, and muscle strength in old mice, while the effects of high-intensity intermittent training are less clear. The study also reveals structural and functional adaptations in skeletal muscle in response to exercise training, as well as age-dependent metabolic remodeling. These findings highlight the importance of tailored exercise prescription for improving health and mitigating age-related muscle strength and function loss in the elderly.
Article
Genetics & Heredity
Melanie Galano, Shereen Ezzat, Vassilios Papadopoulos
Summary: This study reports the first patient with a heterozygous SCP2 mutation leading to SCPx deficiency. The patient exhibited clinical symptoms including progressive brainstem neurodegeneration, cardiac dysrhythmia, muscle wasting, and azoospermia. Analysis of fatty acids, protein expression, and metabolic pathways suggested the association of SCPx deficiency with various metabolic processes. Treatment interventions increasing SCPx levels may have therapeutic potential for reversing the effects of SCPx deficiency.
Article
Cell Biology
Magdalena Juhaszova, Evgeny Kobrinsky, Dmitry B. Zorov, H. Bradley Nuss, Yael Yaniv, Kenneth W. Fishbein, Rafael de Cabo, Lluis Montoliu, Sandra B. Gabelli, Miguel A. Aon, Sonia Cortassa, Steven J. Sollott
Summary: ATP synthase can utilize both Delta psi(m)-driven H+- and K+-transport to synthesize ATP under physiological conditions. The presence of K+ increases ATP synthesis rate in isolated mitochondria while also increasing oxygen consumption rate. The data obtained from purified F1Fo single molecule experiments are consistent with the functional data observed in intact mitochondria.
Article
Cell Biology
Magdalena Juhaszova, Evgeny Kobrinsky, Dmitry B. Zorov, H. Bradley Nuss, Yael Yaniv, Kenneth W. Fishbein, Rafael de Cabo, Lluis Montoliu, Sandra B. Gabelli, Miguel A. Aon, Sonia Cortassa, Steven J. Sollott
Summary: ATP synthase serves as the primary way for K+ to enter mitochondria, and its activity can be upregulated by endogenous survival-related proteins via IF1. The interaction between IF1 and Bcl-xL or Mcl-1 enhances ATP synthase's efficiency and limits ischemia-reperfusion injury.