Article
Biochemistry & Molecular Biology
Tianyang Lan, Kang Zhang, Feifei Lin, Qifu He, Shenghui Wu, Zhiming Xu, Yong Zhang, Fusheng Quan
Summary: MICU1 modulators enhance mitochondrial activity, pyruvate metabolism, and developmental competence of thawed oocytes after vitrification. Vitrification leads to adverse effects on mitochondrial function, but these effects can be mitigated by MICU1 activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, General & Internal
Robert J. Unwin
Summary: Toxic nephropathy, a growing concern, is often caused by new drugs and polypharmacy. Patients' lack of knowledge about their medications and the prevalence of unapproved drugs contribute to the problem. Early detection, drug withdrawal, and supportive care are crucial for effective treatment.
EUROPEAN JOURNAL OF INTERNAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Kyle S. McCommis, Brian N. Finck
Summary: Pyruvate is a crucial metabolic product that needs to be transported to the mitochondrial matrix for energy utilization or to become the building block of new biomolecules. The mitochondrial pyruvate carrier (MPC) has emerged as a target for therapeutic intervention in diseases related to altered mitochondrial and intermediary metabolism. In this review, the role of MPC and related metabolic pathways in the liver in regulating energy metabolism and the current state of targeting this pathway to treat liver diseases are discussed. Inhibiting MPC in hepatocytes and other liver cells has shown beneficial effects in treating type 2 diabetes and nonalcoholic steatohepatitis, although there are still gaps in our understanding of the pleiotropic effects of MPC inhibition.
Review
Biochemistry & Molecular Biology
Lawrence H. Lash
Summary: Mitochondria in renal proximal tubular cells play various key roles, including ATP synthesis, regulation of redox status, initiation of mitophagy and apoptosis. The membrane transport mechanisms of glutathione and its derivatives across the mitochondrial inner membrane are critical for these functions and may serve as targets for therapeutic approaches. Detecting specific components released by renal mitochondria into urine or extracellular medium could serve as indicators of exposure to nephrotoxicants before irreversible renal injury occurs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Claire Pujol, Elise Lebigot, Pauline Gaignard, Said Galai, Ichraf Kraoua, Jean-Philippe Bault, Rodolphe Dard, Ilhem Ben Youssef-Turki, Souheil Omar, Audrey Boutron, Timothy Wai, Abdelhamid Slama
Summary: This study identifies pathogenic variants in the MPC2 gene associated with human disease in four patients from two unrelated families. These variants disrupt pyruvate import into mitochondria, leading to impaired mitochondrial metabolism and neurological dysfunction.
Article
Biochemistry & Molecular Biology
Kevin Wang, Amanda Moore, Cathryn Grayson, Ryan J. Mailloux
Summary: In this study, it was found that pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase (KGDH) are important sources of hydrogen peroxide (H2O2) and key sites for redox regulation. The inhibition of KGDH by S-nitroso-glutathione (GSNO) is more sensitive compared to PDH, and the deactivation of both enzymes by nitro modification is affected by sex and diet. Overall, this study demonstrates for the first time that GSNO deactivates H2O2 production by α-keto acid dehydrogenases and shows that sex and diet are determinants for the nitro-inhibition of both KGDH and PDH.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Yi-Ming Guan, Zong-Li Diao, Hong-Dong Huang, Jun-Fang Zheng, Qi-Dong Zhang, Li-Yan Wang, Wen-Hu Liu
Summary: The study demonstrates that apelin protects tubular mitochondria and improves renal functions in AKI through Sirt3 upregulation. Apelin treatment reverses abnormal protein expression in mitochondria, increases ATP levels, and alleviates kidney damage in the AKI model. Additionally, apelin administration normalizes kidney function markers and may have potential renoprotective effects in treating AKI to retard CKD progression.
Article
Pharmacology & Pharmacy
Kristan H. Cleveland, Rick G. Schnellmann
Summary: Mitochondrial dysfunction is responsible for the development and progression of diabetic kidney disease (DKD). This study investigates the signaling mechanisms through which the beta 2-adrenergic receptor (AR) agonist formoterol restores mitochondrial fission/fusion proteins Drp1 and Mfn1. The results show that formoterol acts through separate but integrated pathways to promote mitochondrial biogenesis, decrease fission, and increase fusion in renal proximal tubule cells (RPTC) treated with high glucose, suggesting its potential as a therapeutic for DKD.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Cell Biology
Yutaro Mori, Amrendra K. Ajay, Jae-Hyung Chang, Shan Mou, Huiping Zhao, Seiji Kishi, Jiahua Li, Craig R. Brooks, Sheng Xiao, Heung-Myong Woo, Venkata S. Sabbisetti, Suetonia C. Palmer, Pierre Galichon, Li Li, Joel M. Henderson, Vijay K. Kuchroo, Julie Hawkins, Takaharu Ichimura, Joseph Bonventre
Summary: Tubulointerstitial abnormalities can predict the progression of diabetic kidney disease, with KIM-1 playing a crucial role in this process. Targeting KIM-1 could be a potential therapeutic approach to alleviate renal damage.
Article
Biology
Aneesha Kohli, Lucie Sauerhering, Sarah K. Fehling, Kevin Klann, Helmut Geiger, Stephan Becker, Benjamin Koch, Patrick C. Baer, Thomas Strecker, Christian Muench
Summary: This study investigated the effects of SARS-CoV-2 and MERS-CoV infections on human renal cells and identified different impacts of these viruses on host cells, which may contribute to renal pathology. The findings revealed important pathways related to innate immune activation and cellular protein quality control, as well as pathways associated with kidney failure that were modulated in response to viral infections.
LIFE SCIENCE ALLIANCE
(2022)
Article
Microbiology
Raquel S. Negreiros, Noelia Lander, Miguel A. Chiurillo, Anibal E. Vercesi, Roberto Docampo
Summary: Pyruvate, the end product of glycolysis, is transported into the mitochondria through the mitochondrial pyruvate carriers MPC1 and MPC2. Knockout of MPC1 and MPC2 in Trypanosoma cruzi affects pyruvate-driven respiration, host cell invasion, and intracellular replication of amastigotes.
Article
Multidisciplinary Sciences
Mei Tang, Yang Zhao, Jianhui Zhao, Shumei Wei, Mingwei Liu, Nairen Zheng, Didi Geng, Shixun Han, Yuchao Zhang, Guoxuan Zhong, Shuaifeng Li, Xiuming Zhang, Chenliang Wang, Huan Yan, Xiaolei Cao, Li Li, Xueli Bai, Junfang Ji, Xin-Hua Feng, Jun Qin, Tingbo Liang, Bin Zhao
Summary: This study generated 25 mouse models of primary liver cancer through in situ genome editing, recapturing major histopathological types of human liver cancer. These models could be divided into three human-matched molecular subtypes based on transcriptomic and proteomic profiles. The study identified various subtype- or genotype-specific alterations in immune micro-environment, metabolic reprogramming, cell proliferation, and drug targets expression. Additionally, the study revealed spatial and temporal dynamics in the expression of pyruvate kinase M2 (Pkm2) through single-cell analysis. Tumor-specific knockdown of Pkm2 reversed the Warburg effect and suppressed tumorigenesis in a genotype-specific manner. This study provides important mouse models of liver cancer with defined genetic drivers and characterized phenotypical heterogeneity for mechanistic investigation and preclinical testing.
Article
Endocrinology & Metabolism
Edoardo Biancalana, Chiara Rossi, Francesco Raggi, Mariarosaria Distaso, Domenico Trico, Simona Baldi, Ele Ferrannini, Anna Solini
Summary: This study aimed to investigate the involvement of NHE3 in modulating the response to sodium glucose co-transporter-2 inhibitors in humans. The results showed that empagliflozin acutely increased urinary pH and induced a substrate shift toward lipid utilization and ketogenesis in healthy young male volunteers, without significant changes in renal NHE3 protein expression.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Gastroenterology & Hepatology
Adam M. Passman, Magnus J. Haughey, Emanuela Carlotti, Marc J. Williams, Bianca Cereser, Meng-Lay Lin, Shruthi Devkumar, Jonathan P. Gabriel, Enrico Gringeri, Umberto Cillo, Francesco Paolo Russo, Matthew Hoare, Joanne ChinAleong, Marnix Jansen, Nicholas A. Wright, Hermant M. Kocher, Weini Huang, Malcolm R. Alison, Stuart A. C. McDonald
Summary: The origin and expansion dynamics of hepatocyte clones in the normal human liver have been determined using lineage tracing, methylation sequence analysis, and next-generation sequencing. Clonal patches of hepatocytes commonly associate with portal tracts and can lineage-trace with cholangiocytes, indicating a common ancestor at this niche. The patterns of mitochondrial DNA variants reveal spatially restricted mutations and limited clonal mutations, indicating slow growth and quiescence of clonal patches.
JOURNAL OF HEPATOLOGY
(2023)
Article
Urology & Nephrology
Milica Bugarski, Susan Ghazi, Marcello Polesel, Joana R. Martins, Andrew M. Hall
Summary: The study found that MA induces AKI mainly through changes in PT NAD and lipid metabolism, leading to acute tubular damage and solute uptake defects in mouse kidney cortex. Treatment strategies such as bicarbonate or nicotinamide can effectively reverse or prevent this pathological process.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Verena Peters, Celine Q. F. Klessens, Hans J. Baelde, Benjamin Singler, Kimberley A. M. Veraar, Ana Zutinic, Jakub Drozak, Johannes Zschocke, Claus P. Schmitt, Emile de Heer
Article
Biochemistry & Molecular Biology
Katarzyna Winiarska, Robert Jarzyna, Jolanta M. Dzik, Adam K. Jagielski, Michal Grabowski, Agata Nowosielska, Dorota Focht, Bartosz Sierakowski
FREE RADICAL BIOLOGY AND MEDICINE
(2015)
Review
Biochemistry & Molecular Biology
Sebastian Kwiatkowski, Anna Kiersztan, Jakub Drozak
CURRENT PROTEIN & PEPTIDE SCIENCE
(2018)
Article
Biology
Sebastian Kwiatkowski, Agnieszka K. Seliga, Didier Vertommen, Marianna Terreri, Takao Ishikawa, Iwona Grabowska, Marcel Tiebe, Aurelio A. Teleman, Adam K. Jagielski, Maria Veiga-da-Cunha, Jakub Drozak
Article
Biology
Qiong Guo, Shanhui Liao, Sebastian Kwiatkowski, Weronika Tomaka, Huijuan Yu, Gao Wu, Xiaoming Tu, Jinrong Min, Jakub Drozak, Chao Xu
Article
Biochemistry & Molecular Biology
Aleksandra Owczarek, Katarzyna Gieczewska, Robert Jarzyna, Adam K. Jagielski, Anna Kiersztan, Andrzej Gruza, Katarzyna Winiarska
Editorial Material
Biochemistry & Molecular Biology
Przemyslaw Bozko
CURRENT MEDICINAL CHEMISTRY
(2020)
Review
Biochemistry & Molecular Biology
Sebastian Kwiatkowski, Jakub Drozak
CURRENT PROTEIN & PEPTIDE SCIENCE
(2020)
Article
Chemistry, Medicinal
Jordi C. J. Hintzen, Laust Moesgaard, Sebastian Kwiatkowski, Jakub Drozak, Jacob Kongsted, Jasmin Mecinovic
Summary: The study presents the development of actin-based peptidomimetics as inhibitors of human SETD3, with selenomethionine-containing beta-actin peptide identified as the most potent inhibitor. Computational docking and molecular dynamics simulations confirmed the rigid His73 binding pocket in SETD3 accommodates the inhibitor peptides with similar binding modes, providing a basis for further development of highly potent and selective SETD3 inhibitors.
Article
Gastroenterology & Hepatology
Grzegorz Oracz, Michal Zarod, Maren Ewers, Helmut Laumen, Tomasz Gambin, Pawel Kaminski, Iwona Grabowska, Anna Drozak, Sebastian Kwiatkowski, Katarzyna Wertheim-Tysarowska, Elwira Kolodziejczyk, Alicja Domaszewicz, Barbara Dorozko, Joanna Kosinska, Stanislaw Gluszek, Dorota Koziel, Rafal Ploski, Jonas Rosendahl, Heiko Witt, Jakub Drozak, Agnieszka Magdalena Rygiel
Summary: The study found that loss of function variants of TRPV6 are associated with increased risk of early-onset CP in Polish and German patients, confirming that TRPV6 is a novel CP susceptibility gene.
Article
Biochemistry & Molecular Biology
Sebastian Kwiatkowski, Maria Bozko, Michal Zarod, Apolonia Witecka, Kubra Kocdemir, Adam K. Jagielski, Jakub Drozak
Summary: This study reports the purification, identification, and biochemical characterization of 4-oxo-L-proline reductase (BDH2) in mammals. Through mass spectrometry analysis, BDH2 was identified as the only candidate for the reductase. The study shows that BDH2 catalyzes the reversible reduction of 4-oxo-L-proline to cis-4-hydroxy-L-proline. These findings are important for understanding the source of cis-4-hydroxy-L-proline in mammalian tissues.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Organic
Nurgul Bilgin, Laust Moesgaard, Marijn N. Maas, Jordi C. J. Hintzen, Apolonia Witecka, Jakub Drozak, Jacob Kongsted, Jasmin Mecinovic
Summary: The role of Ile71 residue in beta-actin on human SETD3 catalysis was examined. It was found that the 'secondary' Ile71 binding pocket regulates the substrate efficiency of beta-actin and can accommodate structurally diverse hydrophobic side chains. Water thermodynamics calculations revealed that high-energy water molecules occupy the Ile71 pocket and are released upon Ile71 binding, contributing to the formation of SETD3-beta A complex. These findings are important for the design and development of chemical probes targeting SETD3.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Review
Biology
Apolonia Witecka, Sebastian Kwiatkowski, Takao Ishikawa, Jakub Drozak
Summary: SETD3 is a histidine methyltransferase specific to actin, known for catalyzing the methylation of H73 residue in human actin or its equivalent in other metazoans. While initially identified as a methyltransferase for histone H3, SETD3's main substrate is now recognized as H73 in actin, contributing to the maintenance of cytoskeleton integrity. Its role in various biological processes, such as cell cycle regulation, apoptosis, carcinogenesis, hypoxic response, and enterovirus pathogenesis, is being increasingly explored.
Article
Biochemistry & Molecular Biology
Giovanni Bisello, Katarzyna Kusmierska, Marcel M. Verbeek, Jolanta Sykut-Cegielska, Michel A. A. P. Willemsen, Ron A. Wevers, Krystyna Szymanska, Jaroslaw Poznanski, Jakub Drozak, Katarzyna Wertheim-Tysarowska, Agnieszka Magdalena Rygiel, Mariarita Bertoldi
Summary: Aromatic amino acid decarboxylase (AADC) deficiency is a rare monogenic disease that causes intellectual disability, movement disorders, and autonomic dysfunction. In this study, a novel mutation of AADC was identified, which resulted in a significant decrease in enzymatic activity. The defect was found to be due to the mispositioning of the catalytically competent intermediate. These findings provide insights into the pathogenesis of AADC deficiency and a potential target for precision therapy.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jordi C. J. Hintzen, Huida Ma, Hao Deng, Apolonia Witecka, Steffen B. Andersen, Jakub Drozak, Hong Guo, Ping Qian, Haitao Li, Jasmin Mecinovic
Summary: This study integrates synthetic, biocatalytic, biostructural, and computational analyses of human SETD3-catalyzed methylation of actin peptides. The findings suggest that SETD3 has a broader substrate scope beyond histidine, including various N-nucleophiles on the aromatic and aliphatic side chains. The research provides insight into the potential of SETD3 to catalyze efficient methylation of several histidine mimics, offering mechanistic and functional understanding of actin histidine methylation.