Article
Microbiology
Jiahui Qian, Tongjie Zhao, Liyu Guo, Senyang Li, Zhengming He, Mingfeng He, Bang Shen, Rui Fang
Summary: Metabolism associated with energy production is compartmentalized in eukaryotic cells, and transporters that move metabolites across organelle membranes play key roles. In this study, researchers identified and characterized two putative ADP/ATP carriers in Toxoplasma gondii. They found that TgAAC1 functions as the mitochondrial ADP/ATP carrier and is critical for parasite growth.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemistry & Molecular Biology
Qiuzi Yi, Shihao Yao, Boyuan Ma, Xiaohui Cang
Summary: This study investigates the structural dynamics of the matrix loops in the ADP/ATP carrier using molecular dynamics simulations. The results reveal interactions between different residues in the matrix loops, as well as the factors determining the initial direction of the loop progression. The study also highlights the significance of conserved residues in the function of the ADP/ATP carrier.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Marina Schock, Steffen Schmidt, Klaus Ersfeld
Summary: Trypanosome brucei, the causative agent of African sleeping sickness, has a highly ordered subpellicular microtubule cytoskeleton associated with various proteins regulating morphology, motility, and virulence. Identified protein CAP50 colocalises with microtubules but not with the flagellum, playing a crucial role in maintaining cellular integrity. Depletion of CAP50, along with CAP52 and CAP42, results in defects in cytokinesis, morphology, and microtubule organization.
Article
Biochemistry & Molecular Biology
Andrew Cowton, Peter Butikofer, Robert Haner, Anant K. Menon
Summary: In this study, two subunits TbGPI14 and TbPBN1 of Trypanosoma brucei GPI-mannosyltransferase-I (GPI-MT-I) were identified as crucial for GPI synthesis and surface expression of GPI-anchored proteins, forming a higher-order complex through interaction. The heterodimeric architecture and species specificity within GPI-MT-I subunit associations were demonstrated with the failure of yeast Gpi14 to restore function in TbGPI14 knockout trypanosomes. The essential role of a trypanosome GPI-MT-I subcomponent indicates wide conservation of the unusual complex structure in glycosyltransferases.
MOLECULAR MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shihao Yao, Boyuan Ma, Qiuzi Yi, Min-Xin Guan, Xiaohui Cang
Summary: The study focuses on the conserved m-gate network in the mitochondrial ADP/ATP carrier, revealing interactions between residues and the promoting effect of CATR on symmetry. These findings provide new insights into the highly conserved yet variable networks within the mitochondrial carrier family.
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
Biochemistry & Molecular Biology
Camila Cimadamore-Werthein, Stephany Jaiquel Baron, Martin S. King, Roger Springett, Edmund R. S. Kunji
Summary: The mitochondrial ADP/ATP carrier plays a crucial role in oxidative phosphorylation by importing ADP into the mitochondrial matrix and exporting ATP. Recent studies have revealed that the carrier functions as a monomer with a single substrate binding site and operates with a ping-pong kinetic mechanism. These findings reconcile the discrepancy between the previous assumptions and provide insights into the alternating access mechanism of the carrier.
Article
Chemistry, Medicinal
Miriam Yague-Capilla, Victor M. Castillo-Acosta, Cristina Bosch-Navarrete, Luis Miguel Ruiz-Perez, Dolores Gonzalez-Pacanowska
Summary: The study characterized the unique trypanosomal SAMHD1 orthologue TbHD52 as essential in maintaining pyrimidine dNTP homeostasis and contributing to cellular dTTP biosynthesis. Knockout of TbHD52 results in cellular dysfunction, which can be rescued by overexpression of human dCMP deaminase.
ACS INFECTIOUS DISEASES
(2021)
Article
Multidisciplinary Sciences
Amit Kumar Gaurav, Marjia Afrin, Xian Yang, Arpita Saha, S. K. Abdus Sayeed, Xuehua Pan, Zeyang Ji, Kam-Bo Wong, Mingjie Zhang, Yanxiang Zhao, Bibo Li
Summary: Trypanosoma brucei is a protozoan parasite that causes human African trypanosomiasis. TbRAP1, a telomere protein, has been shown to silence VSG genes by binding to dsDNA. However, the mechanism by which TbRAP1 allows the expression of a single active VSG gene was unknown. In this study, the researchers unexpectedly discovered an RNA Recognition Motif (RRM) in TbRAP1, which is unprecedented for RAP1 homologs. They found that TbRAP1 RRM, assisted by a specific patch, can recognize and bind to the 3'UTR sequences of VSG genes. Mutating the conserved residues in RRM abolished RNA binding activity, significantly decreased the level of active VSG RNA, and derepressed silent VSG genes. Their findings suggest a monoallelic expression mechanism for VSG genes, in which the abundant RNA of the active VSG gene antagonizes TbRAP1's silencing effect.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Ambre M. Bertholet, Andrew M. Natale, Paola Bisignano, Junji Suzuki, Andriy Fedorenko, James Hamilton, Tatiana Brustovetsky, Lawrence Kazak, Ryan Garrity, Edward T. Chouchani, Nickolay Brustovetsky, Michael Grabe, Yuriy Kirichok
Summary: Mitochondria generate heat through H+ leakage mediated by UCP1 and AAC. Protonophores induce H+ leakage, but their clinical application is limited. This study directly measured the effect of protonophores on H+ leakage and found that it is dependent on AAC and UCP1. Through molecular structure analysis and mathematical modeling, a mechanism of uncoupler-dependent H+ leakage through AAC is proposed.
Article
Biochemistry & Molecular Biology
Katherine Sortino, Brianna L. Tylec, Runpu Chen, Yijun Sun, Laurie K. Read
Summary: Uridine insertion/deletion RNA editing is a common post-transcriptional modification in kinetoplastid organisms. The RESC complex plays an important role in this process by modulating protein and RNA interactions. In this study, the roles of RESC13 and RESC14 are further explored using high-throughput sequencing on multiple transcripts. The findings suggest that RESC13 and RESC14 have both conserved and transcript-specific effects in editing.
Article
Biochemistry & Molecular Biology
Shihao Yao, Qiuzi Yi, Boyuan Ma, Xiaoting Mao, Ye Chen, Min-Xin Guan, Xiaohui Cang
Summary: Through molecular dynamics simulations and sequence analysis, this study reveals a highly specific ADP binding site in the ADP/ATP carrier (AAC), explaining its unusually high substrate specificity and specific substrate selectivity for ADP. This finding provides new insights into the transport mechanism of AAC and other adenine nucleotide transporters, opening up new directions for further research.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Microbiology
Nuria W. Negrao, Logan P. Crowe, Brian S. Mantilla, Rodrigo P. Baptista, Sharon King-Keller, Guozhong Huang, Roberto Docampo
Summary: Trypanosoma brucei is the causative agent of African trypanosomiasis, and there is a need for new drugs due to limited treatment options and evidence of resistance. A phosphoinositide phospholipase C (TbPI-PLC-like) with an X and PDZ domain was discovered, similar to TbPI-PLC1. Recombinant TbPI-PLC-like does not hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP2) and does not modulate TbPI-PLC1 activity, but its knockdown affects the proliferation of trypanosomes.
Article
Microbiology
Caroline E. Dewar, Aitor Casas-Sanchez, Constentin Dieme, Aline Crouzols, Lee R. Haines, Alvaro Acosta-Serrano, Brice Rotureau, Achim Schnaufer
Summary: This study demonstrates that efficient energy production through mitochondria is critical for the trypanosome's swimming ability and migration within the tsetse fly. Surprisingly, trypanosomes with impaired mitochondrial energy production are only mildly compromised in their ability to colonize the tsetse fly midgut. This study provides new insights into the complex mechanisms of trypanosome infection in tsetse flies.
Article
Biochemistry & Molecular Biology
Darline Dize, Rolland Bantar Tata, Rodrigue Keumoe, Rufin Marie Kouipou Toghueo, Mariscal Brice Tchatat, Cyrille Ngansop Njanpa, Vianey Claire Tchuenguia, Lauve Tchokouaha Yamthe, Patrick Valere Tsouh Fokou, Benoit Laleu, James Duffy, Ozlem Tastan Bishop, Fabrice Fekam Boyom
Summary: Novel drugs are urgently needed for the treatment of human African trypanosomiasis (HAT). In this study, a small library of antitrypanosomal analogs was screened, and two potent analogs were identified, showing much higher activity than the parent hit. These two analogs have potential as starting points for further drug development.
Review
Cell Biology
Shreya Ahana Ayyub, Fei Gao, Robert N. Lightowlers, Zofia M. Chrzanowska-Lightowlers
JOURNAL OF CELL SCIENCE
(2020)
Article
Biochemistry & Molecular Biology
Chau-Duy-Tam Vo, Julie Michaud, Sylvie Elsen, Bruno Faivre, Emmanuelle Bouveret, Frederic Barras, Marc Fontecave, Fabien Pierrel, Murielle Lombard, Ludovic Pelosi
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Fei Gao, Frank Voncken, Claudia Colasante
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
(2020)
Article
Environmental Sciences
Kathryn J. Bowen, Nabreesa Murphy, Sarah Dickin, Adis Dzebo, Charles Ebikeme
Summary: The research evaluated the framing of human health within international agendas addressing global challenges and emphasized the importance of health systems strengthening in integrating health issues across these agendas. Findings highlighted limited synergies among health themes and the absence of a governance mechanism to support the integration of multiple agendas for effective national level implementation, emphasizing the crucial role of health leadership.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2021)
Article
Microbiology
Katayoun Kazemzadeh, Mahmoud Hajj Chehade, Gautier Hourdoir, Camille Dorothee Brunet, Yvan Caspar, Laurent Loiseau, Frederic Barras, Fabien Pierrel, Ludovic Pelosi
Summary: The study identified UQ(8) as the major quinone in Francisella novicida and showed that UQ is essential for the bacterial growth in respiratory medium. The results suggest that selective inhibitors of bacterial UQ biosynthesis could be valuable for controlling the pathogenicity of Francisella.
JOURNAL OF BACTERIOLOGY
(2021)
Review
Clinical Neurology
May Yung Tiet, Zhiyuan Lin, Fei Gao, Matthew James Jennings, Rita Horvath
Summary: LS, the most common pediatric clinical presentation of mitochondrial disease, is highly heterogeneous in its clinical phenotype. While historically treatment has been supportive, new therapies are emerging. However, due to the rarity of LS, large-scale interventional studies are limited, with evidence largely remaining in case reports and case series.
JOURNAL OF NEUROMUSCULAR DISEASES
(2021)
Article
Clinical Neurology
Semra Hiz Kurul, Yavuz Oktay, Ana Topf, Nora Zs Szabo, Serdal Gungor, Ahmet Yaramis, Ece Sonmezler, Leslie Matalonga, Uluc Yis, Katherine Schon, Ida Paramonov, Ipek Polat Kalafatcilar, Fei Gao, Aliz Rieger, Nur Arslan, Elmasnur Yilmaz, Burcu Ekinci, Pinar Pulat Edem, Mahmut Aslan, Bilge Ozgor, Angela Lochmuller, Ashwati Nair, Emily O'Heir, Alysia K. Lovgren, Reza Maroofian, Henry Houlden, Kiran Polavarapu, Andreas Roos, Juliane S. Muller, Denisa Hathazi, Patrick F. Chinnery, Steven Laurie, Sergi Beltran, Hanns Lochmueller, Rita Horvath
Summary: Consanguineous marriages in Turkey have a prevalence rate of 24% and pose an increased risk of genetic diseases. Previous limitations in diagnostic options have been overcome through whole exome sequencing, resulting in causative variants being identified in 72% of the families studied. Furthermore, the discovery of novel genes in 14% of the families has increased the diagnostic yield.
Review
Biotechnology & Applied Microbiology
Fabien Pierrel, Arthur Burgardt, Jin-Ho Lee, Ludovic Pelosi, Volker F. Wendisch
Summary: This article reviews the discovery and regulation of the CoQ biosynthesis pathway and summarizes the metabolic engineering strategies for the overproduction of CoQ by microorganisms. Studies have revealed the details of CoQ biosynthesis and the existence of multiprotein complexes composed of several enzymes in different species. Currently, only microorganisms that naturally synthesize CoQ have been used for biotechnological production, but with the exploration of new strategies, microbial CoQ production is expected to improve.
WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY
(2022)
Article
Genetics & Heredity
Sebastian Cristian Treitli, Priscila Pena-Diaz, Pawel Halakuc, Anna Karnkowska, Vladimir Hampl
Summary: Monocercomonoides exilis is considered the first eukaryote known to lack mitochondria completely. By re-sequencing the genome and transcriptome, the contiguity of the genome assembly was improved, leading to better gene prediction, but no mitochondrial hallmark genes were identified, further supporting the hypothesis of mitochondrial absence.
MICROBIAL GENOMICS
(2021)
Article
Biochemistry & Molecular Biology
Arthur Burgardt, Ludovic Pelosi, Mahmoud Hajj Chehade, Volker F. Wendisch, Fabien Pierrel
Summary: This study demonstrates the successful improvement of heterologous CoQ10 production strain by engineering Corynebacterium glutamicum. The strain showed increased CoQ10 content and titer, while reducing the accumulation of other isoprenologs.
Article
Biochemistry & Molecular Biology
Justyna Zitek, Zoltan Fussy, Sebastian C. Treitli, Priscila Pena-Diaz, Zuzana Vaitova, Daryna Zavadska, Karel Harant, Vladimir Hampl
Summary: The loss of mitochondria in oxymonad protists is related to the redirection of the essential Fe-S cluster assembly to the cytosol. However, as our understanding of diverse free-living protists expands, the list of functions of their mitochondrial-related organelles (MROs) also expands. By accurately analyzing the proteome of the MRO in Paratrimastix pyriformis, a close relative of oxymonads, we discovered another function, which involves the production of folate derivatives with one-carbon units and formate. These derivatives are likely to be used by the cytosolic methionine cycle.
Article
Biochemistry & Molecular Biology
Justyna Zitek, Martin S. King, Priscila Pen, Eva Pyrihov, Alannah C. King, Edmund R. S. Kunji, Vladimir Hampl
Summary: Paratrimastix pyriformis is a free-living flagellate belonging to the group Metamonada and it has a mitochondrion-related organelle involved in one-carbon folate metabolism. The organelle contains solute carrier family 25 (SLC25) members responsible for metabolite exchange across the mitochondrial inner membrane. PpMC1, the adenine nucleotide carrier, was shown to transport ATP, ADP, and to a lesser extent, AMP, but not phosphate. It represents a distinct class of adenine nucleotide carriers different from ADP/ATP carriers and ATP-Mg/phosphate carriers.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Clinical Neurology
Lindsay A. Wilson, William L. Macken, Luke D. Perry, Christopher J. Record, Katherine Schon, Rodrigo S. S. Frezatti, Sharika Raga, Kireshnee Naidu, Ozlem Yayici Koken, Ipek Polat, Musambo M. Kapapa, Natalia Dominik, Stephanie Efthymiou, Heba Morsy, Melissa Nel, Mahmoud R. Fassad, Fei Gao, Krutik Patel, Maryke Schoonen, Michelle Bisschoff, Armand Vorster, Hallgeir Jonvik, Ronel Human, Elsa Lubbe, Malebo Nonyane, Seena Vengalil, Saraswati Nashi, Kosha Srivastava, Richard J. L. F. Lemmers, Alisha Reyaz, Rinkle Mishra, Ana Topf, Christina I. Trainor, Elizabeth C. Steyn, Amokelani C. Mahungu, Patrick J. van der Vliet, Ahmet Cevdet Ceylan, A. Semra Hiz, Busranur Cavdarli, C. Nur Semerci Gunduz, Gulay Gulec Ceylan, Madhu Nagappa, Karthik B. Tallapaka, Periyasamy Govindaraj, Silvere M. van der Maarel, Gayathri Narayanappa, Bevinahalli N. Nandeesh, Somwe Wa Somwe, David R. Bearden, Michelle P. Kvalsund, Gita M. Ramdharry, Yavuz Oktay, Uluc Yis, Haluk Topaloglu, Anna Sarkozy, Enrico Bugiardini, Franclo Henning, Jo M. Wilmshurst, Jeannine M. Heckmann, Robert McFarland, Robert W. Taylor, Izelle Smuts, Francois H. van der Westhuizen, Claudia Ferreira da Rosa Sobreira, Pedro J. Tomaselli, Wilson Marques, Rohit Bhatia, Ashwin Dalal, M. V. Padma Srivastava, Sireesha Yareeda, Atchayaram Nalini, Venugopalan Y. Vishnu, Kumarasamy Thangaraj, Volker Straub, Rita Horvath, Patrick F. Chinnery, Robert D. S. Pitceathly, Francesco Muntoni, Henry Houlden, Jana Vandrovcova, Mary M. Reilly, Michael G. Hanna
Summary: This study established a remote transcontinental partnership to evaluate the genetic architecture of neuromuscular diseases in diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counseling, improving care pathways, and making patients eligible for gene-specific trials. Similar virtual partnerships could be adopted in other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients worldwide.
Article
Biochemistry & Molecular Biology
Sophie Saphia Abby, Katayoun Kazemzadeh, Charles Vragniau, Ludovic Pelosi, Fabien Pierrel
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2020)
