Article
Medicine, Research & Experimental
Aiora Cenigaonandia-Campillo, Roberto Serna-Blasco, Laura Gomez-Ocabo, Sonia Solanes-Casado, Natalia Banos-Herraiz, Laura Del Puerto-Nevado, Jose Antonio Canas, Maria Jesus Acenero, Jesus Garcia-Foncillas, Oscar Aguilera
Summary: The study revealed a significant role of vitamin C in regulating pyruvate dehydrogenase (PDH) activity, thus modulating the TCA cycle and mitochondrial metabolism in KRAS mutant colon cancer. Vitamin C downregulated PDK-1 expression in KRAS mutant CRC cells and murine xenografts by reducing proline hydroxylation of HIF-1α, leading to decreased GLUT-1 expression.
Article
Biochemistry & Molecular Biology
Non Miyata, Takanori Ito, Miyu Nakashima, Satoru Fujii, Osamu Kuge
Summary: The Ups2-Mdm35 complex plays an important role in mitochondrial energy metabolism and cell quiescence entry through its involvement in phospholipid synthesis. Depletion of Ups2 leads to overactivation of the yeast AMPK homolog Snf1, which in turn affects mitochondrial ATP production and cell quiescence entry. Additionally, depletion of Ups2 in yeast results in synthetic growth defects when combined with the cell-cycle regulators Whi5 and Whi7, similar to the functional orthologs of the tumor suppressor Rb1. Knockdown of the human homolog of Ups2, PRELID3b, also reduces the viability of Rb1-deficient breast cancer cells, suggesting its potential as a target for cancer therapy.
Article
Biochemistry & Molecular Biology
Xiaobo Wang, Gongbo Guo, Jinru Zhang, Nicolas Aebez, Zhaohui Liu, Chun-Feng Liu, Christopher A. Ross, Wanli W. Smith
Summary: The study found that mutations in the TMEM230 gene lead to neurodegeneration and impaired mitochondrial transport, highlighting the critical role of maintaining TMEM230 protein levels for neuron survival and axon transport. These findings suggest that mutant TMEM230-induced impairment of mitochondrial transport could be an early event in the development of Parkinson's disease, leading to neuronal injury and degeneration.
HUMAN MOLECULAR GENETICS
(2021)
Article
Multidisciplinary Sciences
Zhiqiang Deng, Xianting Li, Marian Blanca Ramirez, Kerry Purtell, Insup Choi, Jia-Hong Lu, Qin Yu, Zhenyu Yue
Summary: The study reveals that autophagy plays a critical role in protecting cells during energy crisis by regulating cell metabolism, specifically through the selective degradation of the PKA inhibitory subunit RI. This selective autophagy process activates PKA, promotes mitochondrial metabolism, and enhances cell survival under glucose deprivation conditions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Boris Pantic, Daniel Ives, Mara Mennuni, Diego Perez-Rodriguez, Uxoa Fernandez-Pelayo, Amaia Lopez de Arbina, Mikel Munoz-Oreja, Marina Villar-Fernandez, Thanh-mai Julie Dang, Lodovica Vergani, Iain G. Johnston, Robert D. S. Pitceathly, Robert McFarland, Michael G. Hanna, Robert W. Taylor, Ian J. Holt, Antonella Spinazzola
Summary: By restricting the availability of glucose and glutamine, the authors have demonstrated that functional mitochondrial DNAs can be propagated while pathological variants are suppressed. The study shows that 2-Deoxy-D-glucose inhibits the replication of mutant mtDNA and glutamine withdrawal suppresses mtDNA synthesis in mutant cells. This highlights the importance of mitochondrial fitness in driving metabolite preference for mtDNA replication, offering potential interventions to suppress pathological mtDNAs.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Daria Shunkina, Anastasia Dakhnevich, Egor Shunkin, Olga Khaziakhmatova, Valeria Shupletsova, Maria Vulf, Alexandra Komar, Elena Kirienkova, Larisa Litvinova
Summary: Obesity is the main cause of metabolic complications and is often accompanied by fatty liver infiltration. In the case of non-alcoholic fatty liver disease (NAFLD), impaired energy metabolism and excess nutrients are common. Mitochondrial dynamics play an important role in regulating energy balance, mitochondrial function, apoptosis, and mitophagy. This study aimed to investigate the impact of gp130 on mitochondrial dynamics in a cellular model of steatohepatitis. Results showed that IL-6/gp130 increased cell viability, expression of NF-kB1 gene, and markers of mitochondrial dynamics in HepG2 cells. However, IL-6 or gp130 decreased the expression of cytoprotector genes. Increased mitochondrial dynamics gene activity protected against cell death in the steatohepatitis model.
Article
Multidisciplinary Sciences
Caroline E. Dewar, Silke Oeljeklaus, Jan Mani, Wignand W. D. Muehlhaeuser, Corinne von Kaenel, Johannes Zimmermann, Torsten Ochsenreiter, Bettina Warscheid, Andre Schneider
Summary: Mitochondrial quality control mechanism in Trypanosoma brucei is characterized by the ablation of ATOM69, which triggers a unique pathway resulting in the degradation of non-imported mitochondrial proteins. This process involves the recruitment of an unknown protein, an E3 ubiquitin ligase, and a ubiquitin-like protein (TbUbL1) and the release of TbUbL1 from the nucleus to the cytosol.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Rui Chen, Tingbin Ma, Shiyue Du, Junyu Luo, Huan Zhang, Xuan Xu, Zhijian Cao, Zhangqi Yuan, Hao Sun, Mugen Liu, Bo Xiong, Qinghua Shi, Jing Yu Liu
Summary: The testis-specific gene 4930590J08Rik plays a crucial role in male reproduction, as evidenced by its unique expression pattern and the phenotypes observed in knockout mice. This gene disruption leads to impairment in spermatogenesis, reduced sperm count, defective acrosome reactions, and decreased sperm motility. The transcriptome analysis of testes from knockout mice revealed metabolic dysregulation, specifically oxidative phosphorylation deficiency and increased reliance on anaerobic glycolysis. These findings provide novel insights into idiopathic male infertility and present 4930590J08Rik knockout mice as a valuable model for further investigations.
Article
Multidisciplinary Sciences
Sung-Jun Park, Faiyaz Ahmad, Robert J. Bahde, Andrew Philp, Jeonghan Kim, Tianjiao Huang, Myung K. Kim, William C. Trenkle, Jay H. Chung
Summary: There are metabolic benefits to activating AMPK, but direct activation can lead to cardiac enlargement. Therefore, alternative ways to activate AMPK without affecting the heart are needed.
Article
Oncology
Lujie Yang, Qin Zhang, Yanli Xiong, Zhaoqian Dang, He Xiao, Qian Chen, Xiaoyan Dai, Lei Zhang, Jianwu Zhu, Dong Wang, Mengxia Li
Summary: This study discovered that apatinib is a direct activator of AMP-activated protein kinase (AMPK), which inhibits de novo fatty acid synthesis in LKB1-mutant NSCLC. The combination of apatinib with exogenous fatty acid restriction shows promise as a treatment method for LKB1-mutant NSCLC. These findings provide a basis for the accurate and combined application of VEGFR-TKIs, including apatinib and anlotinib, in the treatment of LKB1-mutant NSCLC.
Article
Biochemistry & Molecular Biology
Sagnika Ghosh, Mohammad Zulkifli, Alaumy Joshi, Manigandan Venkatesan, Allen Cristel, Neelanjan Vishnu, Muniswamy Madesh, Vishal M. Gohil
Summary: This study demonstrates the importance of mitochondrial phospholipid cardiolipin in the stability and activity of the mitochondrial calcium uniporter (MCU) complex regulatory subunit MICU1 in Barth syndrome patients. The decrease in MICU1 levels disrupts mitochondrial calcium uptake kinetics, leading to the impairment of pyruvate dehydrogenase activation and reducing equivalents generation, ultimately affecting mitochondrial bioenergetics. Defects in mitochondrial calcium signaling may contribute to cardiac and skeletal muscle pathologies in Barth syndrome patients, highlighting a potential therapeutic target for this disorder.
HUMAN MOLECULAR GENETICS
(2022)
Article
Cell Biology
Hitomi Yamamoto-Imoto, Satoshi Minami, Tatsuya Shioda, Yurina Yamashita, Shinsuke Sakai, Shihomi Maeda, Takeshi Yamamoto, Shinya Oki, Mizuki Takashima, Tadashi Yamamuro, Kyosuke Yanagawa, Ryuya Edahiro, Miki Iwatani, Mizue So, Ayaka Tokumura, Toyofumi Abe, Ryoichi Imamura, Norio Nonomura, Yukinori Okada, Donald E. Ayer, Hidesato Ogawa, Eiji Hara, Yoshitsugu Takabatake, Yoshitaka Isaka, Shuhei Nakamura, Tamotsu Yoshimori
Summary: This study identifies MondoA as a transcription factor that regulates cellular senescence, autophagy, and mitochondrial homeostasis. It shows that MondoA protects against cellular senescence by activating autophagy and suppressing a negative regulator, Rubicon. Furthermore, the study highlights the importance of Prdx3 as a downstream regulator of MondoA in maintaining mitochondrial homeostasis and autophagy. The findings suggest that MondoA decline exacerbates senescence and age-associated diseases.
Article
Marine & Freshwater Biology
Jiawen Cui, Yuhao Liu, Zhiyu Hao, Yuhang Liu, Minna Qiu, Lu Kang, Xiaohua Teng, You Tang
Summary: In this experiment, a poisoning model of common carp with cadmium (Cd) exposure was established to assess the nephrotoxicity of Cd. Results showed that Cd exposure induced kidney injury and had an impact on mitochondrial damage and apoptosis. This study provides insights into the underlying mechanisms and theoretical basis for evaluating Cd toxicity to aquatic organisms.
AQUATIC TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Chiu-Yueh Hung, Chuanshu Zhu, Farooqahmed S. Kittur, Maotao He, Erland Arning, Jianhui Zhang, Asia J. Johnson, Gurpreet S. Jawa, Michelle D. Thomas, Tomas T. Ding, Jiahua Xie
Summary: The pathophysiology of Huntington's disease (HD), caused by the mutant huntingtin protein (mHtt), is still not fully understood. This study explored the early pathogenic events induced by expanded polyglutamine tracts in plants and mice models. The findings suggest that impaired GTP cyclohydrolase I (GTPCH) expression and folate metabolism may play a role in the pathogenesis of HD.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Multidisciplinary Sciences
Mahmoud A. Bassal, Saumya E. Samaraweera, Kelly Lim, Brooks A. Bernard, Sheree Bailey, Satinder Kaur, Paul Leo, John Toubia, Chloe Thompson-Peach, Tran Nguyen, Kyaw Ze Ya Maung, Debora A. Casolari, Diana G. Iarossi, Ilaria S. Pagani, Jason Powell, Stuart Pitson, Siria Natera, Ute Roessner, Ian D. Lewis, Anna L. Brown, Daniel G. Tenen, Nirmal Robinson, David M. Ross, Ravindra Majeti, Thomas J. Gonda, Daniel Thomas, Richard J. D'Andrea
Summary: This study reveals the mutual exclusivity between germline mutations in mitochondrial complex I and somatic mutations in the metabolic enzyme IDH1 in patients with acute myeloid leukemia (AML), and finds that IDH1 mutant cells have increased sensitivity to complex I inhibitors.
NATURE COMMUNICATIONS
(2022)
Article
Gastroenterology & Hepatology
Nicole L. Mancini, Sruthi Rajeev, Timothy S. Jayme, Arthur Wang, Asa Keita, Matthew L. Workentine, Samira Hamed, Johan D. Soderholm, Fernando Lopes, Timothy E. Shutt, Jane Shearer, Derek M. McKay
Summary: LF82 E coli infection caused significant disruption of epithelial mitochondrial function and structure, leading to mitochondrial fragmentation and dysfunction. Inhibitors targeting mitochondrial fission partially reduced the observed effects, suggesting potential strategies to maintain cellular homeostasis and mitigate infection-induced epithelial barrier dysfunction.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Multidisciplinary Sciences
Fahad Iqbal, Marcus Pehar, Andrew J. Thompson, Urva Azeem, Kiana Jahanbakhsh, Nerea Jimenez-Tellez, Rasha Sabouny, Shadab Batool, Atika Syeda, Jennifer Chow, Pranav Machiraju, Timothy Shutt, Kamran Yusuf, Jane Shearer, Tiffany Rice, Naweed Syed
Summary: Anesthetics are necessary for surgical procedures, but can have neurotoxic effects which may be mitigated by protecting mitochondrial networks and inhibiting mitochondrial fission. This study compares the effects of three key anesthetics on neonatal rat cortical neurons under identical conditions, showing their impact on neuronal viability, neurite outgrowth, and synaptic assembly. The findings underscore the importance of designing mitigation strategies to protect against anesthetic-induced toxicity by targeting mitochondria in both animals and humans.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Michelle Grace Acoba, Ebru S. Selen Alpergin, Santosh Renuse, Lucia Fernandez-del-Rio, Ya-Wen Lu, Oleh Khalimonchuk, Catherine F. Clarke, Akhilesh Pandey, Michael J. Wolfgang, Steven M. Claypool
Summary: The study revealed that SFXN1 plays a crucial role in mitochondrial respiratory chain by participating in heme and α-ketoglutarate metabolism, in addition to its known function as a mitochondrial serine transporter.
Review
Biology
Govinda Sharma, Gerald Pfeffer, Timothy E. Shutt
Summary: Mitochondria are dynamic organelles capable of fusing, dividing, and moving within cells, with special importance in neurons due to their high energy demand and unique morphological properties. Dysfunction in mitochondrial dynamics can lead to various neurological disorders, including peripheral neuropathy associated with impaired mitochondrial function. The underlying mechanisms specifically affecting peripheral neurons' sensitivity to impaired mitochondrial dynamics are not fully understood, but there is a focus on pathogenic variants in proteins mediating mitochondrial fusion, fission, and transport as potential causes. Additionally, impaired mitochondrial quality control is highlighted as a key theme linking mitochondrial dysfunction and neuropathies.
Article
Cell Biology
Whitney F. Alpaugh, Anna L. Voigt, Rkia Dardari, Lin Su, Iman Al Khatib, Wisoo Shin, Taylor M. Goldsmith, Krysta M. Coyle, Lin A. Tang, Timothy E. Shutt, Claudia Klein, Jeff Biernaskie, Ina Dobrinski
Summary: The absence of UCH-L1 impacts the maintenance of SSC homeostasis and metabolism, leading to reduced capacity for supporting spermatogenesis and fertility. This study contributes to further understanding the complex regulatory circuits underlying SSC function.
Article
Cell Biology
Anahita Nejatfard, Nicholas Wauer, Satarupa Bhaduri, Adam Conn, Saroj Gourkanti, Narinderbir Singh, Tiffany Kuo, Rachel Kandel, Rommie E. Amaro, Sonya E. Neal
Summary: A recent study identified a new protein, Dfm1, that plays a key role in retrotranslocation process, with conserved residues critical for this function. Additionally, it was found that Dfm1 possesses lipid thinning function to facilitate the removal of ER membrane substrates, a feature also conserved in its human homolog, Derlin-1.
Article
Biochemistry & Molecular Biology
Emily Wachoski-Dark, Tian Zhao, Aneal Khan, Timothy E. Shutt, Steven C. Greenway
Summary: There is a unclear mechanistic link between human mitochondrial disorders and the development of cardiomyopathy. Defects in mitochondrial proteostasis, which involves the maintenance of mitochondrial protein homeostasis, can lead to mitochondrial cardiomyopathies. Disruptions in proteostasis can result in mitochondrial dysfunction and impact cardiac function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Rasha Sabouny, Timothy E. Shutt
Summary: Mitochondria are dynamic organelles that can change their function according to cellular demands. Research has shown that impairments in mitochondrial fusion and fission can impact mtDNA, but the exact relationship between remodeling mitochondrial network morphology and mtDNA remains unclear. Further studies are needed to understand this relationship and its implications for human diseases.
JOURNAL OF CELL SCIENCE
(2021)