Article
Biochemistry & Molecular Biology
Sanja Skulj, Zlatko Brkljaca, Jurgen Kreiter, Elena E. Pohl, Mario Vazdar
Summary: Molecular dynamics simulations of uncoupling proteins present a challenge due to the lack of available structural data. In this study, a combination of homology modelling and MD simulations of UCP2 revealed a structure impermeable to water. Additionally, results from conductance measurements in model membranes suggest that the UCP2 structure modeled from ANT protein possesses key functional elements related to proton transport.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Furkan E. Oflaz, Zhanat Koshenov, Martin Hirtl, Olaf A. Bachkoenig, Wolfgang F. Graier, Benjamin Gottschalk
Summary: Mitochondrial uncoupling proteins UCP1 and UCP2 have different molecular mechanisms for executing their mitochondria uncoupling function, with UCP1 dissipating the proton motive force and UCP2 modulating the permeability of the cristae junction. This mini-review discusses the molecular mechanisms of UCP1 in brown adipose tissue and UCP2 in aged and cancer non-excitable cells, and the synergistic effects of both UCPs with the mitochondrial Ca2+ uptake machinery.
Letter
Plant Sciences
Philippe Fuchs, Elisenda Feixes-Prats, Paulo Arruda, Elias Feitosa-Araujo, Alisdair R. Fernie, Christopher Grefen, Sophie Lichtenauer, Nicole Linka, Ivan de Godoy Maia, Andreas J. Meyer, Soeren Schilasky, Lee J. Sweetlove, Stefanie Wege, Andreas P. M. Weber, A. Harvey Millar, Olivier Keech, Igor Florez-Sarasa, Pedro Barreto, Markus Schwarzlaender
Summary: UCP2 is localized to the Golgi, unlike its close homolog UCP1, which is abundant in the mitochondria.
Article
Biochemistry & Molecular Biology
Chen Feng, Etienne Empweb Anger, Xiong Zhang, Shengdi Su, Chenlin Su, Shuxin Zhao, Feng Yu, Ji Li
Summary: This study suggests that UCP2 may protect HK-2 cells from the toxicity induced by AA I, and reduce the toxicity by decreasing oxidative stress and apoptosis. UCP2 could be a potential target for alleviating AA I-induced nephrotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Plant Sciences
Mariana de Lara Campos Arcuri, Alessandra Vasconcellos Nunes-Laitz, Romulo Pedro Macedo Lima, Pedro Barreto, Andressa Nagatani Marinho, Paulo Arruda, Ivan G. Maia
Summary: This study investigated the potential roles of two UCP genes in Arabidopsis thaliana in energy metabolism, root growth, fertility, and ROS homeostasis. Mutants exhibited alterations in ATP/ADP ratios, reduced respiratory rate, and compromised fertility. Increased hydrogen peroxide accumulation in reproductive organs and disturbed ROS homeostasis were observed, indicating the importance of AtUCP1 and AtUCP2 in flower oxidative homeostasis and overall plant fertility.
PLANT AND CELL PHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
David G. Nicholls
Summary: This review examines the mechanisms underlying non-shivering thermogenesis in brown adipose tissue mediated by UCP1, emphasizing the experimental evidence and physiological constraints. It also discusses the nature of endogenous proton leak and evaluates the troubled history of putative novel uncoupling proteins UCP2 and UCP3.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2021)
Article
Oncology
Haowen Jiang, Clifford Jiajun He, Albert Li, Bo He, Yang Li, Meng-Ning Zhou, Jiangbin Ye
Summary: This study demonstrates that mitochondrial uncoupling effectively inhibits the reductive carboxylation in cancer cells. By activating the electron transport chain and increasing the NAD(+)/NADH ratio, mitochondrial uncoupling accelerates the oxidative tricarboxylic acid cycle and blocks reductive carboxylation. Inhibiting reductive carboxylation could be a key mechanism by which mitochondrial uncouplers inhibit tumor growth.
MOLECULAR CANCER RESEARCH
(2023)
Article
Oncology
Martin R. Weiser, Meier Hsu, Philip S. Bauer, William C. Chapman, Ivan A. Gonzalez, Deyali Chatterjee, Deepak Lingam, Matthew G. Mutch, Ajaratu Keshinro, Jinru Shia, Efsevia Vakiani, Tsuyoshi Konishi, Yoshifumi Shimada, Zsofia Stadler, Neil H. Segal, Andrea Cercek, Leonard Saltz, Rona Yaeger, Anna Varghese, Maria Widmar, Iris H. Wei, Emmanouil P. Pappou, J. Joshua Smith, Garrett Nash, Philip Paty, Julio Garcia-Aguilar, Mithat Gonen
Summary: Clinical calculators and nomograms are recommended by the AJCC for providing individualized and accurate estimates of patient outcome. A third-generation clinical calculator was developed to predict cancer recurrence following resection of stage I-III colon cancer, demonstrating improved discrimination and predictive accuracy by incorporating new variables such as microsatellite genomic phenotype and tumor-infiltrating lymphocytes.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Cell Biology
Sunad Rangarajan, Morgan L. Locy, Diptiman Chanda, Ashish Kurundkar, Deepali Kurundkar, Jennifer L. Larson-Casey, Pilar Londono, Rushita A. Bagchi, Brian Deskin, Hanan Elajaili, Eva S. Nozik, Jessy S. Deshane, Jaroslaw W. Zmijewski, Oliver Eickelberg, Victor J. Thannickal
Summary: This study provides evidence that elevated levels of the mitochondrial protein UCP2 are associated with age-related diseases, such as idiopathic pulmonary fibrosis. UCP2 is shown to contribute to the generation of reactive oxygen species and altered cellular bioenergetics, as well as induce myofibroblast senescence. The findings suggest that targeting UCP2 could be a potential therapeutic strategy for age-related diseases associated with impaired tissue regeneration and organ fibrosis.
Article
Cell Biology
Sumati Hasani, Lyndsay E. A. Young, Warren Van Nort, Moumita Banerjee, Dylan R. Rivas, Jinhwan Kim, Xiaopeng Xiong, Ramon C. Sun, Matthew S. Gentry, Hiromi Sesaki, Tianyan Gao
Summary: Loss of Drp1 activates compensative metabolic pathways, glucose uptake and glycogenesis, to promote cell survival in colon cancer.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Yangyang Lei, Tianzhu Yu, Changyu Li, Jianke Li, Yicheng Liang, Xinyuan Wang, Yi Chen, Xiaolin Wang
Summary: This study investigated the expression and clinical significance of CAMK1 in pancreatic cancer. Results showed that CAMK1 was highly expressed in PC and had prognostic value in PC patients. Protein-protein interaction analysis identified several important genes associated with CAMK1, suggesting a potential role of CAMK1 as a candidate marker for investigating clinical prognosis of PC.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Kyung-Taek Kang, Min-Joo Shin, Hye-Ji Moon, Kyung-Un Choi, Dong-Soo Suh, Jae-Ho Kim
Summary: This study found that TRRAP overexpression increases NANOG protein stability and enhances the tumorigenic potential of colon cancer stem cells. TRRAP inhibits the ubiquitination degradation of NANOG by binding to it. TRRAP knockdown decreases the expression of CD44, a cancer stem cell marker, and increases the expression of P53, a tumor suppressor gene, in colon cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Md. Reyad-ul-Ferdous, Yongfeng Song
Summary: Further studies are required in both murine and human models to understand the full mechanism of action by mitochondrial modulation. Drug development investigation also requires the development of a precise formulation.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Francesco De Leonardis, Amer Ahmed, Angelo Vozza, Loredana Capobianco, Christopher L. Riley, Simona Nicole Barile, Daria Di Molfetta, Stefano Tiziani, John Digiovanni, Luigi Palmieri, Vincenza Dolce, Giuseppe Fiermonte
Summary: UCP3 catalyzes a strict exchange of aspartate, malate, sulphate, and phosphate, with R282Q mutation abolishing its transport activity. UCP3 differs from UCP2 in transport mode and kinetic constants.
Article
Multidisciplinary Sciences
Berna Somuncu, Aysegul Ekmekcioglu, Fatma Merve Antmen, Tugce Ertuzun, Emre Deniz, Nazli Keskin, Joon Park, Ilgu Ece Yazici, Busra Simsek, Batu Erman, Whitney Yin, Burak Erman, Meltem Muftuoglu
Summary: Synthetic lethality in DNA repair pathways is an important strategy for treating cancer. In this study, a synthetic lethal interaction between MLH1 and Poly was used for selective treatment of MLH1 deficient cancers. The Poly inhibitor, CR, was found to selectively kill MLH1 deficient cancer cells and inhibit tumor growth.