Article
Biochemistry & Molecular Biology
Lawrence H. Lash
Summary: Previous studies have shown that overexpression of transporters can reduce cellular susceptibility to chemicals. However, this study found that overexpression of the mitochondrial 2-oxoglutarate carrier (OGC) increased cellular injury from the antineoplastic drug cisplatin.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Plant Sciences
Arnaud Fertet, Stefanie Graindorge, Sandrine Koechler, Gert-Jan de Boer, Emilie Guilloteau-Fonteny, Jose M. Gualberto
Summary: The mtDNA variation among Lactuca species is minimal, with L. serriola showing significant differences from other species, suggesting it may be the direct ancestor of cultivated lettuce. Additionally, a close phylogenetic relationship between the mtDNA of L. sativa and L. virosa was found, indicating a hybridization event between L. virosa and the ancestor of cultivated lettuce led to the mitochondrial genome of L. sativa.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Ekaterina S. Kharechkina, Anna B. Nikiforova, Alexey G. Kruglov
Summary: The opening of the permeability transition pore (PTP) in mitochondria is a crucial event in cell death initiation, especially in conditions like ischemia/reperfusion. K+ transport into mitochondria has a protective effect against ischemia/reperfusion, but its role in PTP regulation is not well understood. In this study, the role of K+ and other monovalent cations in the regulation of PTP opening was investigated using an in vitro model. The results suggest that the stimulation of PTP opening by cations involves the suppression of K+/H+ exchange and acidification of the matrix, facilitating the influx of phosphate.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Endocrinology & Metabolism
Sotiria Tavoulari, Denis Lacabanne, Chancievan Thangaratnarajah, Edmund R. S. Kunji
Summary: Citrin deficiency is a globally prevalent mitochondrial disease with three stages: neonatal intrahepatic cholestasis, a mild adaptation stage, and adult citrullinemia. It is caused by the absence or dysfunction of the calcium-regulated mitochondrial aspartate/glutamate carrier 2 (AGC2/SLC25A13), also known as citrin. This deficiency affects the malate-aspartate shuttle, gluconeogenesis, amino acid homeostasis, and the urea cycle.
TRENDS IN ENDOCRINOLOGY AND METABOLISM
(2022)
Article
Biotechnology & Applied Microbiology
Huong N. Vu, Diana M. Downs
Summary: This study reveals a mechanism in Salmonella enterica for salvaging phosphorylated B-6 vitamers utilizing the periplasmic phosphatase PhoN. The findings suggest a unique strategy for energy conservation in species across domains of life and shed light on the general role of promiscuous phosphatases and kinases in organismal fitness.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Rami Mosaoa, Anna Kasprzyk-Pawelec, Harvey R. Fernandez, Maria Laura Avantaggiati
Summary: The mitochondrial citrate/isocitrate carrier (CIC) plays a crucial role in human diseases by facilitating the transport of ions and metabolites through the mitochondrial membrane, impacting mitochondrial metabolism and respiration. Additionally, CIC also serves various fundamental activities in the cytosol, such as acting as a metabolic substrate, an allosteric enzymatic regulator, and an epigenetic modifier.
Article
Biochemistry & Molecular Biology
Nhung Thi Nguyen, Tuyet Thi Nguyen, Ha Thu Nguyen, Ji-Min Lee, Min-Ji Kim, Xu-Feng Qi, Seung-Kuy Cha, In-Kyu Lee, Kyu-Sang Park
Summary: Blocking the transport of phosphate ions into mitochondria could prevent blood vessel stiffening, which is a major risk factor for cardiovascular disease. Researchers found that phosphate transport proteins in mitochondria triggered harmful reactions that led to vascular stiffening. Inhibition of these proteins' activity reduced pathological changes and highlighted the therapeutic potential for treating vascular calcification associated with hyperphosphatemia.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Maria Petrosino, Karim Zuhra, Jola Kopec, Andrew Hutchin, Csaba Szabo, Tomas Majtan
Summary: In this study, the binding and inhibitory mechanism of the CBS inhibitor AOAA were characterized. It was found that AOAA can be replaced by serine, which allows for the continuation of the catalytic cycle. Serine rescued the activity and function of AOAA-inhibited CBS. The results demonstrate the complexity of using AOAA as a CBS inhibitor and highlight the need for a potent, selective, and specific pharmacological CBS inhibitor.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Endocrinology & Metabolism
Natalie M. Garza, Abhinav B. Swaminathan, Krishna P. Maremanda, Mohammad Zulki Fli, Vishal M. Gohil
Summary: Copper is an essential micronutrient that plays a crucial role in mitochondrial energy metabolism. Copper enters cells through transporters and is distributed to cuproenzymes by chaperones. Mutations in copper transporters and chaperones disrupt copper homeostasis in mitochondria, leading to genetic disorders. Elesclomol, a copper ionophore, shows therapeutic potential for copper deficiency disorders.
TRENDS IN ENDOCRINOLOGY AND METABOLISM
(2023)
Review
Biochemistry & Molecular Biology
Annamaria Tonazzi, Nicola Giangregorio, Lara Console, Ferdinando Palmieri, Cesare Indiveri
Summary: The SLC25A20 transporter, also known as the carnitine acyl-carnitine carrier (CAC), plays a crucial role in the transport of short, medium, and long carbon chain acyl-carnitines. Despite the lack of a clear 3D structure, CAC is one of the most extensively studied transport proteins in the inner mitochondrial membrane. Post-translational modifications have been found to regulate the transport activity of CAC, which can be influenced by drugs, toxic substances, and dietary compounds.
Review
Biochemistry & Molecular Biology
Mariana Fernandez-Caggiano, Philip Eaton
Summary: The mitochondrial pyruvate carrier (MPC) plays a crucial role in determining the fate of pyruvate in cells, with decreased expression contributing to lactate accumulation in the cytosol. Reduced MPC abundance has also been observed in failing hearts, suggesting a potential causal role in heart failure progression.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Cell Biology
Jessica N. Peoples, Nasab Ghazal, Duc M. Duong, Katherine R. Hardin, Janet R. Manning, Nicholas T. Seyfried, Victor Faundez, Jennifer Q. Kwong
Summary: Mitochondria can trigger various signaling pathways under stress conditions, with mitochondrial energy dysfunction leading to a pattern of acylome remodeling. This remodeling specifically impacts mitochondrial proteins, with acetylation and malonylation modifying the interactome and enzyme activity within mitochondria. Additionally, a novel cross talk between acetylation and malonylation was discovered, indicating a mechanism by which disruption to energy production can impact global mitochondrial function.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Article
Microbiology
Soomin Choi, Gyunghwa Jeong, Eunna Choi, Eun-Jin Lee
Summary: Bacteria use two-component systems to sense and respond to their environment. The PhoU protein, along with other components, plays a role in phosphate signaling in Gram-negative bacteria. PhoU is believed to function as a negative regulator in phosphate signaling, but its exact mechanism is not fully understood. This study identified specific residues in PhoU that interact with the PhoR histidine kinase and found that these interactions control the expression of pho genes in different phosphate and Mg2+ concentrations. Furthermore, it was discovered that PhoU's role in promoting PhoR autophosphorylation is required for Salmonella virulence.
Article
Chemistry, Medicinal
Liang Xu, Clyde F. Phelix, Liao Y. Chen
Summary: This study developed de novo models of human MPC complexes and characterized the conformational dynamics of the MPC1/2 heterodimer. It was found that functional MPC1/2 tends to adopt an inward-open conformation and can regulate pyruvate transport by stably binding to substrate or inhibitor.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
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
Cell Biology
Xin Chen, Xinxin Song, Jingbo Li, Ruoxi Zhang, Chunhua Yu, Zhuan Zhou, Jiao Liu, Siyan Liao, Daniel J. Klionsky, Guido Kroemer, Jinbao Liu, Daolin Tang, Rui Kang
Summary: This study identifies HPCAL1 as a novel autophagy receptor for the selective degradation of CDH2 during ferroptosis. Depletion of CDH2 increases susceptibility to ferroptotic death. The phosphorylation of HPCAL1 and the non-classical LC3-interacting region motif play key roles in the autophagic degradation of CDH2. A ferroptosis inhibitor is found to suppress HPCAL1 expression. Inhibition of HPCAL1 prevents ferroptosis-induced tumor suppression and pancreatitis in mouse models.
Review
Gastroenterology & Hepatology
Amir Ajoolabady, Neil Kaplowitz, Cynthia Lebeaupin, Guido Kroemer, Randal J. Kaufman, Harmeet Malhi, Jun Ren
Summary: The endoplasmic reticulum stress and unfolded protein response play important roles in the pathophysiology of liver diseases. Understanding this process is crucial for developing interventions for the treatment of nonmalignant liver diseases.
Editorial Material
Cell Biology
Omar Motino, Flavia Lambertucci, Gerasimos Anagnostopoulos, Sijing Li, Isabelle Martins, Guido Kroemer
Summary: DBI/ACBP acts as a paracrine inhibitor of autophagy and its neutralization by a monoclonal antibody has cytoprotective effects on various organs. This study reveals a potentially useful strategy for enhancing autophagy by targeting DBI/ACBP, and provides new insights into the protective mechanisms of autophagy in organ damage.
Article
Cell Biology
Lea Montegut, Adrien Joseph, Hui Chen, Mahmoud Abdellatif, Christoph Ruckenstuhl, Omar Motino, Flavia Lambertucci, Gerasimos Anagnostopoulos, Sylvie Lachkar, Silvia Dichtinger, Maria Chiara Maiuri, Francois Goldwasser, Benoit Blanchet, Frederic Fumeron, Isabelle Martins, Frank Madeo, Guido Kroemer
Summary: Autophagy defects accelerate aging, while activation of autophagy slows down aging. Acyl-coenzyme A binding protein (ACBP), encoded by diazepam-binding inhibitor (DBI), acts as an extracellular regulator of autophagy. Knockout of ACBP gene in yeast improves chronological aging, and this effect is reversed by knockout of autophagy genes but less so by knockout of mitophagy gene. In humans, ACBP levels correlate with body mass index (BMI) and age, with high ACBP levels predicting future cardiovascular events independently of BMI and age. ACBP plasma concentrations in mice are associated with cardiovascular risk factors and can be attenuated by a monoclonal antibody, suggesting its prognostic value in cardiovascular disease.
Editorial Material
Cell Biology
Lea Montegut, Adrien Joseph, Hui Chena, Mahmoud Abdellatif, Christoph Ruckenstuhlg, Isabelle Martins, Frank Madeo, Guido Kroemer
Summary: DBI/ACBP is a conserved paracrine inhibitor that regulates autophagy and lifespan. Its increased levels in humans are associated with biological age and cardiovascular disease risk factors. Studies have shown that neutralizing DBI/ACBP can alleviate cardiac aging. Therefore, it may serve as a potential target for treating age-associated cardiovascular diseases.
Article
Cell Biology
Qian Xue, Ding Yan, Xi Chen, Xiaofen Li, Rui Kang, Daniel J. J. Klionsky, Guido Kroemer, Xin Chen, Daolin Tang, Jinbao Liu
Summary: Ferroptosis is an iron-dependent regulated cell death characterized by lipid peroxidation and membrane damage. Copper promotes ferroptotic cell death by inducing autophagic degradation of GPX4. These findings provide new insights into the connection between metal stress and autophagy-dependent cell death.
Review
Medicine, Research & Experimental
Lorenzo Galluzzi, Oliver Kepp, Erik Hett, Guido Kroemer, Francesco M. Marincola
Summary: Mammalian cells can undergo regulated cell death in response to specific disruptions of homeostasis, leading to adaptive immune responses. This immunogenic cell death (ICD) is distinct from immunostimulation or inflammatory responses that do not depend on cellular demise. In this article, we critically discuss the key concepts and mechanisms of ICD and its implications for cancer immunotherapy.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Editorial Material
Oncology
Oliver Kepp, Peng Liu, Laurence Zitvogel, Guido Kroemer
Editorial Material
Oncology
Oliver Kepp, Hui Pan, Peng Liu, Guido Kroemer
Editorial Material
Oncology
Oliver Kepp, Laurence Zitvogel, Guido Kroemer
Summary: In a recent paper in Science, Chen et al. conducted genetic engineering to produce S. epidermidis strains that express tumor cross-reactive antigens. Topical administration of these strains triggered T cell responses and exhibited anticancer effects. Here, the authors discussed both the direct local effects and indirect systemic effects of exposure to engineered S. epidermidis strains.
Review
Oncology
Jenny Sprooten, Raquel S. Laureano, Isaure Vanmeerbeek, Jannes Govaerts, Stefan Naulaerts, Daniel M. Borras, Lisa Kinget, Jitka Fucikova, Radek Spisek, Lenka Palova Jelinkova, Oliver Kepp, Guido Kroemer, Dmitri V. Krysko, An Coosemans, Rianne D. W. Vaes, Dirk De Ruysscher, Steven De Vleeschouwer, Els Wauters, Evelien Smits, Sabine Tejpar, Benoit Beuselinck, Sigrid Hatse, Hans Wildiers, Paul M. Clement, Peter Vandenabeele, Laurence Zitvogel, Abhishek D. Garg
Summary: Immunogenic cell death (ICD) is a unique process of regulated cell death that activates the immune system. The effectiveness of ICD relies on the antigenicity of dying cells and their ability to expose immunostimulatory molecules. Certain chemotherapies, such as anthracyclines, paclitaxels, and oxaliplatin, have been validated as potent ICD inducers and can be used in combination with immunotherapies against resistant tumors. This article discusses the integration of ICD-inducing chemotherapy in immuno-oncological paradigms.
Article
Cell Biology
Mathilde Coulet, Sylvie Lachkar, Marion Leduc, Marc Trombe, Zelia Gouveia, Franck Perez, Oliver Kepp, Guido Kroemer, Stephane Basmaciogullari
Summary: In this study, a selective hook system called RUSH was used to identify cell secretion modulators in U2OS cells. They created a U2OS cell line that expressed a modified antibody bait and a streptavidin hook, which allowed the antibody to be retained in the endoplasmic reticulum (ER). Biotin was used to trigger the release of the antibody from the ER, resulting in its secretion.
Article
Cell Biology
Safae Terrisse, Laurence Zitvogel, Guido Kroemer
Summary: Recent observations show that hormone-receptor breast cancer is influenced by immune and microbial factors. The immune system retards the development of hormone-positive breast cancer and affects the efficacy of hormone therapy. The gut microbiota modulates the anticancer immune response, tumor microenvironment, and estrogen metabolism. Understanding these mechanisms is still in its early stages and requires further analysis.
Editorial Material
Oncology
Oliver Kepp, Peng Liu, Guido Kroemer, Lorenzo Galluzzi
Summary: BCL2 robustly maintains mitochondrial integrity, inhibits immune signaling and cell death, and limits the ability of dendritic cells to initiate adaptive immune responses, suggesting a universal immunosuppressive function for the mitochondrial immune checkpoint.
