Article
Cell Biology
Lingna Yi, Xue-Jun Shang, Linglu Lv, Yixiang Wang, Jingjing Zhang, Chao Quan, Yuqin Shi, Yunhao Liu, Ling Zhang
Summary: Cadmium induces apoptosis of mouse Leydig cells through excessive mitochondrial fission and inhibition of mitophagy, which is associated with disruption of mitochondrial function and elevated levels of mitochondrial superoxide and cellular ROS.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Jingjing Pan, Yanfeng Wei, Linlin Ni, Xiaoyang Li, Yu Deng, Bin Xu, Tianyao Yang, Jingyi Sun, Wei Liu
Summary: This study investigates the role of calcium ion (Ca2+) homeostasis in MeHg-induced neurotoxicity. The results suggest that MeHg causes cell damage and increases Ca2+ release from the ER as well as free Ca2+ levels in the cytoplasm and mitochondria. Ca2+ channel inhibitors and Ca2+ chelator can partially inhibit MeHg-induced mitochondrial damage and apoptosis.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2022)
Article
Biology
Vivian W. R. Moraes, Vivian M. Santos, Eloah R. Suarez, Leticia S. Ferraz, Rayssa de Mello Lopes, Giuliana P. Mognol, Joana D. Campeiro, Joao A. Machado-Neto, Fabio D. Nascimento, Mirian A. F. Hayashi, Ivarne L. S. Tersariol, Donald D. Newmeyer, Tiago Rodrigues
Summary: Mitochondria play crucial roles in cellular physiology, and their dysregulation has been linked to cancer cells. Thioridazine (TR) induces cytotoxicity in human leukemia cells through a mechanism involving calcium imbalance, mitochondrial permeabilization, endoplasmic reticulum stress, and apoptosis. Additionally, TR shows potential as an adjuvant in antitumor chemotherapy.
Article
Cell Biology
Benjamin Cartes-Saavedra, Josefa Macuada, Daniel Lagos, Duxan Arancibia, Maria E. Andres, Patrick Yu-Wai-Man, Gyoergy Hajnoczky, Veronica Eisner
Summary: Autosomal Dominant Optic Atrophy (ADOA), caused by OPA1 mutations, affects Ca2+ homeostasis by modulating ER-mitochondria coupling, potentially contributing to the progression of ADOA.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Shanliang Zheng, Dong Zhao, Guixue Hou, Song Zhao, Wenxin Zhang, Xingwen Wang, Li Li, Liang Lin, Tie-Shan Tang, Ying Hu
Summary: The study demonstrates the interaction between TMCO1 and iASPP in colon cancer, affecting tumor growth and cell apoptosis by modulating Ca2+ homeostasis. Intervention in the iASPP-TMCO1 axis can effectively inhibit tumor progression.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
David M. Booth, Peter Varnai, Suresh K. Joseph, Gyorgy Hajnoczky
Summary: The study shows that individual mitochondria generate oxidative bursts at interorganellar contact sites, with Ca2+ channels directly sensing these bursts and responding with transient Ca2+ transients. Under mitochondrial stress or apoptotic stimuli, the frequency and amplitude of the oxidative bursts can be increased.
Article
Multidisciplinary Sciences
Mate Katona, Adam Bartok, Zuzana Nichtova, Gyorgy Csordas, Elena Berezhnaya, David Weaver, Arijita Ghosh, Peter Varnai, David Yule, Gyorgy Hajnoczky
Summary: The study reveals that the IP3 receptor traffics in and out of ER-Mitochondria contacts, and when trapped, enhances calcium signaling to stimulate energy metabolism.
NATURE COMMUNICATIONS
(2022)
Review
Multidisciplinary Sciences
Wenping Wu, Jimin Zheng, Zongchao Jia
Summary: The mitochondrial uniporter is a Ca2+-selective ion-conducting channel in the inner mitochondrial membrane composed of MCU, MCUb, EMRE, MICU1, and MICU2. Recent structural studies have provided insights into the component structures and their spatial relationship, contributing to a better understanding of mitochondrial Ca2+ uptake and regulation. Further research in this area could lead to advancements in studying mitochondrial Ca2+ permeation and related diseases.
Article
Biochemistry & Molecular Biology
Giovanni Quarato, Fabien Llambi, Cliff S. Guy, Jaeki Min, Marisa Actis, Huan Sun, Shilpa Narina, Shondra M. Pruett-Miller, Junmin Peng, Zoran Rankovic, Douglas R. Green
Summary: The imbalance of intracellular Ca2+ and mitochondrial Ca2+ overload can lead to mitochondrial inner membrane permeabilization and cell death, which is distinct from Bcl-2 family-regulated mitochondrial outer membrane permeabilization. Cyclosporin A can prevent cell death by inhibiting Ca2+ release from endoplasmic reticulum stores.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Multidisciplinary Sciences
Marilen Federico, Maite Zavala, Tamara Vico, Sofia Lopez, Enrique Portiansky, Silvia Alvarez, Maria Celeste Villa Abrille, Julieta Palomeque
Summary: The study reveals that prediabetic myocardium induced by a fructose-rich diet undergoes remodeling in SR-mitochondria microdomains, involving SR-Ca2+ leak and mitochondrial fission, leading to abnormal mitochondrial structure and metabolism.
SCIENTIFIC REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Shuheng Wen, Toshihiko Aki, Takeshi Funakoshi, Kana Unuma, Koichi Uemura
Summary: This review discusses the neurotoxic effects of cocaine and the role of mitochondrial dynamics in cellular physiology. It highlights how cocaine can disrupt neuronal mitochondrial dynamics and impair cellular function. Understanding and studying the relationship between mitochondrial dynamics and cocaine exposure is crucial for exploring the mechanisms of cocaine neurotoxicity and potential therapeutic interventions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Alexis Martinez, Cristian M. Lamaizon, Cristian Valls, Fabien Llambi, Nancy Leal, Patrick Fitzgerald, Cliff Guy, Marcin M. Kaminski, Nibaldo C. Inestrosa, Brigitte van Zundert, Gonzalo I. Cancino, Andres E. Dulcey, Silvana Zanlungo, Juan J. Marugan, Claudio Hetz, Douglas R. Green, Alejandra R. Alvarez
Summary: Endoplasmic reticulum stress activates c-Abl tyrosine kinase, which translocates to mitochondria. Activated c-Abl interacts with mitochondrial fusion protein MFN2, leading to mitochondrial fragmentation and apoptosis.
Article
Biochemistry & Molecular Biology
Yu-Shen Luo, Quan-Kuo He, Ming-Xin Sun, Feng-Xin Qiao, Yue-Cen Liu, Chang-Long Xu, Zhi-Ran Xu, Si-Cheng Zhao, Hai-Long Wang, Zhong-Quan Qi, Yu Liu
Summary: Acrylonitrile treatment disrupts ovarian homeostasis, leading to impaired follicular development and reduced offspring. This is associated with inflammation, apoptosis, DNA damage, oxidative stress, endoplasmic reticulum abnormalities, and lysosomal aggregation caused by acrylonitrile exposure.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Pharmacology & Pharmacy
Lei Kuang, Yu Zhu, Yue Wu, Xiaoyong Peng, Kunlun Tian, Liangming Liu, Tao Li
Summary: The combination of PBA and CsA showed beneficial effects in septic shock by improving tissue perfusion, organ function, and survival rates. PBA enhanced CsA-induced cardiovascular protection, leading to a synergistic therapeutic effect.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Applied
Zhi-Feng Tan, Yue Ding, Jing-Yu Tian, Zi-Qiang Liu, Jing-Ran Bi, Da-Yong Zhou, Liang Song, Gui-Bing Chen
Summary: UV irradiation caused various changes in sea cucumber coelomocytes, including calcium imbalance and abnormal morphology of the endoplasmic reticulum. Injection of the calcium chelator helped maintain intracellular calcium homeostasis in sea cucumbers and suppressed other abnormal changes. Apoptosis in sea cucumbers is mediated by calcium imbalance and follows the activation of the ER stress pathway.
Article
Biochemistry & Molecular Biology
Marta Zaninello, Konstantinos Palikaras, Aggeliki Sotiriou, Nektarios Tavernarakis, Luca Scorrano
Summary: Mitochondrial dysfunction and mitophagy are common characteristics of neurodegenerative diseases, and in ADOA, mitophagy depends on Ca2+-calcineurin-AMPK signaling cascade, providing insights into the pathogenesis of this disease.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Cell Biology
Silvia Graziani, Luca Scorrano, Giovanna Pontarin
Summary: Doxorubicin is an effective antineoplastic drug, but its serious cardiotoxic side effects can lead to heart failure. This study reveals that transient exposure to Doxorubicin can cause long-term downregulation of VEGFR2 in endothelial cells, which is essential for their function. The downregulation is not dependent on autophagy, but rather on Doxorubicin-induced p53 expression and inhibition of protein synthesis.
Article
Biochemistry & Molecular Biology
Ricardo Sanchez-Rodriguez, Caterina Tezze, Andrielly H. R. Agnellini, Roberta Angioni, Francisca C. Venegas, Chiara Cioccarelli, Fabio Munari, Nicole Bertoldi, Marcella Canton, Maria Andrea Desbats, Leonardo Salviati, Rosanna Gissi, Alessandra Castegna, Maria Eugenia Soriano, Marco Sandri, Luca Scorrano, Antonella Viola, Barbara Molon
Summary: Macrophages play essential roles in host defense against pathogens, inflammation regulation, and tissue regeneration. OPA1, a mitochondria-shaping protein, is shown to be a key metabolic driver in macrophage activation.
CELL DEATH AND DIFFERENTIATION
(2023)
Review
Biochemistry & Molecular Biology
Ilio Vitale, Federico Pietrocola, Emma Guilbaud, Stuart A. Aaronson, John M. Abrams, Dieter Adam, Massimiliano Agostini, Patrizia Agostinis, Emad S. Alnemri, Lucia Altucci, Ivano Amelio, David W. Andrews, Rami Aqeilan, Eli Arama, Eric H. Baehrecke, Siddharth Balachandran, Daniele Bano, Nickolai A. Barlev, Jiri Bartek, Nicolas G. Bazan, Christoph Becker, Francesca Bernassola, Mathieu J. M. Bertrand, Marco E. Bianchi, Mikhail V. Blagosklonny, J. Magarian Blander, Giovanni Blandino, Klas Blomgren, Christoph Borner, Carl D. Bortner, Pierluigi Bove, Patricia Boya, Catherine Brenner, Petr Broz, Thomas Brunner, Rune Busk Damgaard, George A. Calin, Michelangelo Campanella, Eleonora Candi, Michele Carbone, Didac Carmona-Gutierrez, Francesco Cecconi, Francis K-M Chan, Guo-Qiang Chen, Quan Chen, Youhai H. Chen, Emily H. Cheng, Jerry E. Chipuk, John A. Cidlowski, Aaron Ciechanover, Gennaro Ciliberto, Marcus Conrad, Juan R. Cubillos-Ruiz, Peter E. Czabotar, Vincenzo D'Angiolella, Mads Daugaard, Ted M. Dawson, Valina L. Dawson, Ruggero De Maria, Bart De Strooper, Klaus-Michael Debatin, Ralph J. Deberardinis, Alexei Degterev, Giannino Del Sal, Mohanish Deshmukh, Francesco Di Virgilio, Marc Diederich, Scott J. Dixon, Brian D. Dynlacht, Wafik S. El-Deiry, John W. Elrod, Kurt Engeland, Gian Maria Fimia, Claudia Galassi, Carlo Ganini, Ana J. Garcia-Saez, Abhishek D. Garg, Carmen Garrido, Evripidis Gavathiotis, Motti Gerlic, Sourav Ghosh, Douglas R. Green, Lloyd A. Greene, Hinrich Gronemeyer, Georg Haecker, Gyorgy Hajnoczky, J. Marie Hardwick, Ygal Haupt, Sudan He, David M. Heery, Michael O. Hengartner, Claudio Hetz, David A. Hildeman, Hidenori Ichijo, Satoshi Inoue, Marja Jaeaettelae, Ana Janic, Bertrand Joseph, Philipp J. Jost, Thirumala-Devi Kanneganti, Michael Karin, Hamid Kashkar, Thomas Kaufmann, Gemma L. Kelly, Oliver Kepp, Adi Kimchi, Richard N. Kitsis, Daniel J. Klionsky, Ruth Kluck, Dmitri Krysko, Dagmar Kulms, Sharad Kumar, Sergio Lavandero, Inna N. Lavrik, John J. Lemasters, Gianmaria Liccardi, Andreas Linkermann, Stuart A. Lipton, Richard A. Lockshin, Carlos Lopez-Otin, Tom Luedde, Marion MacFarlane, Frank Madeo, Walter Malorni, Gwenola Manic, Roberto Mantovani, Saverio Marchi, Jean-Christophe Marine, Seamus J. Martin, Jean-Claude Martinou, Pier G. Mastroberardino, Jan Paul Medema, Patrick Mehlen, Pascal Meier, Gerry Melino, Sonia Melino, Edward A. Miao, Ute M. Moll, Cristina Munoz-Pinedo, Daniel J. Murphy, Maria Victoria Niklison-Chirou, Flavia Novelli, Gabriel Nunez, Andrew Oberst, Dimitry Ofengeim, Joseph T. Opferman, Moshe Oren, Michele Pagano, Theocharis Panaretakis, Manolis Pasparakis, Josef M. Penninger, Francesca Pentimalli, David M. Pereira, Shazib Pervaiz, Marcus E. Peter, Paolo Pinton, Giovanni Porta, Jochen H. M. Prehn, Hamsa Puthalakath, Gabriel A. Rabinovich, Krishnaraj Rajalingam, Kodi S. Ravichandran, Markus Rehm, Jean-Ehrland Ricci, Rosario Rizzuto, Nirmal Robinson, Cecilia M. P. Rodrigues, Barak Rotblat, Carla Rothlin, David C. Rubinsztein, Thomas Rudel, Alessandro Rufini, Kevin M. Ryan, Kristopher A. Sarosiek, Akira Sawa, Emre Sayan, Kate Schroder, Luca Scorrano, Federico Sesti, Feng Shao, Yufang Shi, Giuseppe S. Sica, John Silke, Hans-Uwe Simon, Antonella Sistigu, Anastasis Stephanou, Brent R. Stockwell, Flavie Strapazzon, Andreas Strasser, Liming Sun, Erwei Sun, Qiang Sun, Gyorgy Szabadkai, Stephen W. G. Tait, Daolin Tang, Nektarios Tavernarakis, Carol M. Troy, Boris Turk, Nicoletta Urbano, Peter Vandenabeele, Tom Vanden Berghe, Matthew G. Vander Heiden, Jacqueline L. Vanderluit, Alexei Verkhratsky, Andreas Villunger, Silvia von Karstedt, Anne K. Voss, Karen H. Vousden, Domagoj Vucic, Daniela Vuri, Erwin F. Wagner, Henning Walczak, David Wallach, Ruoning Wang, Ying Wang, Achim Weber, Will Wood, Takahiro Yamazaki, Huang-Tian Yang, Zahra Zakeri, Joanna E. Zawacka-Pankau, Lin Zhang, Haibing Zhang, Boris Zhivotovsky, Wenzhao Zhou, Mauro Piacentini, Guido Kroemer, Lorenzo Galluzzi
Summary: Apoptosis is a regulated cell death process involving caspase family proteases. Inhibiting or delaying apoptosis experimentally through pharmacological and genetic strategies has demonstrated its importance in embryonic development, tissue homeostasis, and the pathogenesis of various human disorders. Defects in apoptotic cell death machinery impair development and promote oncogenesis, while inappropriate activation of apoptosis contributes to cell loss and tissue damage in neurological, cardiovascular, renal, hepatic, infectious, neoplastic, and inflammatory conditions.
CELL DEATH AND DIFFERENTIATION
(2023)
Review
Biochemistry & Molecular Biology
Ruben Quintana-Cabrera, Luca Scorrano
Summary: Mitochondria are not only central organelles in metabolism and energy conversion but also platforms for cellular signaling cascades. The shape and ultrastructure of mitochondria are dynamically regulated by mitochondria-shaping proteins, and their alterations in human diseases can be explored for drug discovery.
Editorial Material
Cell Biology
Satoko Shinjo, Luca Scorrano
Summary: Receptor-mediated endocytosis transports LDLs to late endosomes, where cholesterol is delivered to mitochondria. Zhou et al. discovered that LDL-containing endosomes fuse with mitochondria, providing cholesterol for steroid biosynthesis and enabling mitochondrial degradation of the LDL receptor.
NATURE CELL BIOLOGY
(2023)
Article
Cell Biology
Masafumi Noguchi, Susumu Kohno, Anna Pellattiero, Yukino Machida, Keitaro Shibata, Norihito Shintani, Takashi Kohno, Noriko Gotoh, Chiaki Takahashi, Atsushi Hirao, Luca Scorrano, Atsuko Kasahara
Summary: Drug resistance is a major challenge in chemotherapy and targeted cancer treatments. This study identifies the mitochondrial protein Opa1 as a participant in gefitinib resistance in lung adenocarcinoma cells. Inhibition of Opa1 restores mitochondrial morphology and sensitizes resistant cells to apoptosis induced by gefitinib. Combination treatment of gefitinib with a specific Opa1 inhibitor reduces tumor size in vivo and increases apoptosis. Targeting Opa1 could be a potential strategy to overcome gefitinib resistance.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Francesco Chemello, Michela Pozzobon, Lorenza Iolanda Tsansizi, Tatiana Varanita, Ruben Quintana-Cabrera, Daniele Bonesso, Martina Piccoli, Gerolamo Lanfranchi, Marta Giacomello, Luca Scorrano, Camilla Bean
Summary: Approved gene therapies for spinal muscular atrophy (SMA) improve SMA natural history but are not curative. Loss of survival motor neuron 1 (SMN1) has detrimental effects in muscle beyond motor neurons, leading to accumulation of dysfunctional mitochondria. Amniotic fluid stem cells transplantation can restore mitochondrial morphology and expression of mitochondrial genes in SMA mouse model, suggesting that targeting muscle mitochondrial dysfunction may complement current gene therapy for SMA.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Caterina Vianello, Federica Dal Bello, Sang Hun Shin, Sara Schiavon, Camilla Bean, Ana Paula Magalhaes Rebelo, Tomas Knedlik, Emad Norouzi Esfahani, Veronica Costiniti, Rodrigo S. Lacruz, Giuseppina Covello, Fabio Munari, Tommaso Scolaro, Antonella Viola, Elena Rampazzo, Luca Persano, Sara Zumerle, Luca Scorrano, Alessio Gianelle, Marta Giacomello
Summary: Recent studies have found a connection between changes in mitochondria physiology and cellular pathophysiological mechanisms, and the function of these organelles needs to be validated. However, a method for high-throughput quantification of mitochondrial membrane potential has not been established yet. In this study, we present a methodology for unbiased quantification of mitochondrial membrane potential in vitro, suitable for various cell models. Our method successfully analyzed mitochondrial membrane potential in different cell types and allowed discrimination between cell subpopulations using automated image analysis and machine learning.
Article
Biochemistry & Molecular Biology
Martina Semenzato, Ludovica Zambello, Stefania Fumarola, Enrico Motta, Luana Piroli, Luca Scorrano, Camilla Bean
Summary: This study presents a simple mechanical dissociation procedure for collecting mesenchymal stem cells and soluble fractions from lipoaspirates. A self-contained cell purification device called IStemRewind was used for one-step purification of cells and soluble material, offering a potential solution for rapid and efficient isolation of MSCs and immunomodulatory soluble factors.
News Item
Oncology
Martina Semenzato, Luca Scorrano
Article
Biochemistry & Molecular Biology
Martina Semenzato, Mark J. Kohr, Charlotte Quirin, Roberta Menabo, Petra Alanova, Lukas Alan, Anna Pellattiero, Elizabeth Murphy, Fabio Di Lisa, Luca Scorrano
Summary: During cardiac ischemia-reperfusion, excessive reactive oxygen species cause damage to mitochondria, cells, and organs. This study reveals that oxidative stress leads to the oxidation of cysteine in the mitochondrial protein Opa1, resulting in mitochondrial damage and cell death. By inhibiting the Opa1 oxidation process, mitochondrial damage and cell death induced by oxidative stress can be reduced independent of mitochondrial fusion.
Article
Physiology
Andre Djalalvandi, Luca Scorrano
Summary: Mitochondrial dynamics play a crucial role in skeletal muscle physiology, where changes can lead to fusion and increased respiratory capacity, while imbalances in dynamics may result in muscle atrophy.
CURRENT OPINION IN PHYSIOLOGY
(2022)
Correction
Biotechnology & Applied Microbiology
Panagiotis Galanos, George Pappas, Alexander Polyzos, Athanassios Kotsinas, Ioanna Svolaki, Nickolaos N. Giakoumakis, Christina Glytsou, Ioannis S. Pateras, Umakanta Swain, Vassilis L. Souliotis, Alexandros G. Georgakilas, Nicholas Geacintov, Luca Scorrano, Claudia Lukas, Jiri Lukas, Zvi Livneh, Zoi Lygerou, Dipanjan Chowdhury, Claus Storgaard Sorensen, Jiri Bartek, Vassilis G. Gorgoulis
Correction
Endocrinology & Metabolism
Camilla Bean, Matteo Audano, Tatiana Varanita, Francesca Favaretto, Marta Medaglia, Marco Gerdol, Lena Pernas, Fabio Stasi, Marta Giacomello, Stephanie Herkenne, Maheswary Muniandy, Sini Heinonen, Emma Cazaly, Miina Ollikainen, Gabriella Milan, Alberto Pallavicini, Kirsi H. Pietilainen, Roberto Vettor, Nico Mitro, Luca Scorrano