Article
Environmental Sciences
Yajuan Lu, Hanyu Tang, Xia Wang, Junjie Xu, Fei Sun
Summary: This study reveals the detrimental effects of dibutyltin dichloride (DBTCl) exposure on mouse oocytes, resulting in decreased follicle and oocyte numbers, inhibited meiotic maturation, impaired spindle assembly and chromosome alignment, and mitochondrial dysfunction leading to the accumulation of reactive oxygen species and induction of apoptosis.
Article
Oncology
Katarina Letkovska, Pavel Babal, Zuzana Cierna, Silvia Schmidtova, Veronika Liskova, Katarina Kalavska, Vera Miskovska, Samuel Horak, Katarina Rejlekova, Michal Chovanec, Jozef Mardiak, Pavel Janega, Michal Mego
Summary: GCTs exhibit lower expression of AIF compared to normal testicular tissue, which could promote cell survival and metastatic dissemination. The downregulation of AIF may serve as a potential therapeutic target in GCTs.
Article
Medicine, General & Internal
Min Ji Kwon, Jeong Nam Kim, Joon Park, Yun Tai Kim, Min Jae Lee, Byung Joo Kim
Summary: The anti-cancer effects of Alisma canaliculatum extracts (ACE) on AGS gastric cancer cells include inhibiting cell growth, inducing apoptosis, and regulating cell death through various signaling pathways.
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
(2021)
Article
Environmental Sciences
Yu-Ting Zhou, Rui Li, Si-Hong Li, Xiang Ma, Lu Liu, Dong Niu, Xing Duan
Summary: Perfluorooctanoic acid (PFOA) exposure during gestation was found to have potential toxic effects on ovarian function and resulted in higher meiotic defects in female offspring. PFOA exposure disrupted early embryonic cleavage and blastocyst formation by impacting spindle assembly and chromosome alignment. Moreover, PFOA exposure caused mitochondrial dysfunction, oxidative stress, DNA damage, autophagy, and apoptosis in 2-cell stage embryos.
ENVIRONMENT INTERNATIONAL
(2022)
Article
Fisheries
Xue Qiao, Lilin Hou, Jihan Wang, Yuhao Jin, Ning Kong, Jialuo Li, Sicong Wang, Lingling Wang, Linsheng Song
Summary: The study identified a homologue of AIF, CgAIF1, in oysters, which shares a similarity of 35.44% to 79.22% with AIF1s from other species. Upon LPS and Poly (I:C) stimulation, the mRNA transcripts of CgAIF1 in gills significantly increased.
FISH & SHELLFISH IMMUNOLOGY
(2021)
Article
Environmental Sciences
Zhi-Ming Ding, Yang-Wu Chen, Muhammad Jamil Ahmad, Yong-Sheng Wang, Sheng-Ji Yang, Ze-Qun Duan, Ming Liu, Cai-Xia Yang, Ai-Xin Liang, Guo-Hua Hua, Li-Jun Huo
Summary: This study investigated the toxicity of Bisphenol F (BPF) on mouse oocyte meiotic maturation and quality. The results showed that BPF could inhibit meiotic progression, disrupt spindle assembly and chromosome alignment, induce oxidative stress and DNA damage, and trigger early apoptosis in mouse oocytes. Furthermore, BPF exposure also led to altered epigenetic modifications. Compared with BPA, BPF had less severe toxic effects on oocyte maturation and spindle structure but induced more DNA damage. In conclusion, BPF is not a safe substitute for BPA.
ENVIRONMENTAL TOXICOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anwesha Bandyopadhyay, Sudip Kumar Ghosh
Summary: Our study shows the presence of a AIF-like protein in a caspase-deficient protozoan, suggesting the occurrence of apoptosis in unicellular organisms. The protein migrates to the nucleus upon stress and is involved in chromatin degradation and condensation. Down-regulating its expression attenuates apoptotic features, while over-expression enhances them. The widely-used drug metronidazole induces similar AIF-mediated cell death, indicating it as a probable mechanism of amoebicidal action. The occurrence of apoptosis in unicellular organisms may signify altruistic death that benefits the population health.
MOLECULAR MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Xiaomin Li, Ting Chen, Xiaofen Wu, Xiao Jiang, Peng Luo, E. Zixuan, Chaoqun Hu, Chunhua Ren
Summary: Apoptosis is a critical biological process for embryonic development, tissue differentiation, and organism homeostasis. A novel apoptosis-inducing factor called AIF-2 has been identified in sea cucumbers, and it is involved in heavy metal-induced apoptosis, contributing to the understanding of the caspase-independent apoptotic pathway in ancient echinoderm species.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Suneela Zaigham, Magnus Dencker, Magnus K. Karlsson, Ola Thorsson, Per Wollmer
Summary: This study found that elevated TRAIL levels are associated with impaired lung function in school-aged children, especially with significant associations with markers of pulmonary airflow obstruction.
RESPIRATORY MEDICINE
(2021)
Article
Cell Biology
Esra Peker, Konstantin Weiss, Jiyao Song, Christine Zarges, Sarah Gerlich, Volker Boehm, Aleksandra Trifunovic, Thomas Langer, Niels H. Gehring, Thomas Becker, Jan Riemer
Summary: Peker et al. discovered a two-step import pathway that allows proteins to be localized to both the matrix and IMS. Weak targeting signals enable proteins to form stabilizing disulfide bonds in the IMS before being imported into the matrix. This pathway enables the monitoring of import activity in both compartments. The study found that NDUFAF8, a factor involved in complex I assembly, follows this two-step import pathway, and its import is regulated by proteases to ensure proper function.
JOURNAL OF CELL BIOLOGY
(2023)
Review
Cell Biology
Juan Rodriguez, Tao Li, Yiran Xu, Yanyan Sun, Changlian Zhu
Summary: This review focuses on the molecular mechanisms of hypoxic-ischemic encephalopathy, specifically highlighting the importance of apoptosis-inducing factor. Understanding the roles of this factor is crucial for developing more effective treatments for perinatal brain injury. Additionally, the interaction of apoptosis-inducing factor with other proteins may provide promising therapeutic targets for improving outcomes after perinatal brain injury.
NEURAL REGENERATION RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Romeo Romagnoli, Delia Preti, Ernest Hamel, Roberta Bortolozzi, Giampietro Viola, Andrea Brancale, Salvatore Ferla, Giampaolo Morciano, Paolo Pinton
Summary: The researchers developed a new series of anticancer agents that induce apoptosis to inhibit cell proliferation. These compounds triggered significant apoptosis in colon cancer cells, with potential effects observed in both metastatic and non-metastatic cells.
BIOORGANIC CHEMISTRY
(2021)
Article
Cell Biology
Shiwei Qiu, Weihao Zhao, Xue Gao, Dapeng Li, Weiqian Wang, Bo Gao, Weiju Han, Shiming Yang, Pu Dai, Peng Cao, Yongyi Yuan
Summary: Mutations in ATP6V1B2 can lead to hearing loss through mechanisms involving genetic compensation of Atp6v1b1 in hair cells and lysosomal dysfunction-induced apoptosis. Experimental evidence from mouse models suggests that the use of apoptosis inhibitors may help improve hearing impairment caused by ATP6V1B2 mutations.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Environmental Sciences
Jingyan Ge, Jian Liu, Taiwei Wang, Di Huang, Junwei Li, Shuang Zhang, Mengqi Wang, Wei Liu, Lijing Zhao
Summary: Long-term exposure to Atrazine (ATR) in rats resulted in increased spleen index, decreased white blood cells, significant reduction in Th1, Th2, and Th17 cells while an increase in Treg cells, changes in cytokine levels, and degenerative changes in the spleen. This suggests that long-term ATR exposure may inhibit immune system function in rats.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Oncology
Tatsushi Yoshida, Kenta Yamasaki, Kenjiro Tadagaki, Yasumichi Kuwahara, Akifumi Matsumoto, Adem Ejub Sofovic, Noriko Kondo, Toshiyuki Sakai, Tsukasa Okuda
Summary: The study identified RUNX1 as a transcriptional regulator of TRAIL, showing that TRAIL expression is decreased in acute myeloid leukemia patients and inhibited by RUNX1-ETO.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2022)
Review
Endocrinology & Metabolism
Michio Hirano, Valerio Carelli, Roberto De Giorgio, Loris Pironi, Anna Accarino, Giovanna Cenacchi, Roberto D'Alessandro, Massimiliano Filosto, Ramon Marti, Francesco Nonino, Antonio Daniele Pinna, Elisa Baldin, Bridget Elizabeth Bax, Alessio Bolletta, Riccardo Bolletta, Elisa Boschetti, Matteo Cescon, Roberto D'Angelo, Maria Teresa Dotti, Carla Giordano, Laura Ludovica Gramegna, Michelle Levene, Raffaele Lodi, Hanna Mandel, Maria Cristina Morelli, Olimpia Musumeci, Alessia Pugliese, Mauro Scarpelli, Antonio Siniscalchi, Antonella Spinazzola, Galit Tal, Javier Torres-Torronteras, Luca Vignatelli, Irina Zaidman, Heinz Zoller, Rita Rinaldi, Massimo Zeviani
Summary: MNGIE is a rare autosomal recessive disease caused by TYMP mutations, leading to gastrointestinal and neurological symptoms. Diagnosis is challenging and treatment options are limited, with a need for standardized monitoring methods.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Maria Jose Perez, Dina Ivanyuk, Vasiliki Panagiotakopoulou, Gabriele Di Napoli, Stefanie Kalb, Dario Brunetti, Rawaa Al-Shaana, Stephan A. Kaeser, Sabine Anne-Kristin Fraschka, Mathias Jucker, Massimo Zeviani, Carlo Viscomi, Michela Deleidi
Summary: Mutations in the PITRM1 gene lead to a slow-progressing syndrome characterized by cerebellar ataxia and cognitive decline. Studies using PITRM1-knockout iPSCs show induction of mitochondrial unfolded protein response and increased mitochondrial clearance in neurons, as well as elevated levels of amyloid precursor protein and amyloid beta. Astrocytes also show dysregulated immune transcriptional signatures in PITRM1-knockout cerebral organoids.
MOLECULAR PSYCHIATRY
(2021)
Review
Biochemistry & Molecular Biology
Michele Brischigliaro, Massimo Zeviani
Summary: COX deficiency is characterized by genetic and phenotypic heterogeneity, affecting the whole organism or specific tissues with different disease onsets. Over 30 genes have been linked to COX deficiency, and research on the enzyme's functional features and phenotypical consequences continues to expand through experimental models.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2021)
Review
Biochemistry & Molecular Biology
Erika Fernandez-Vizarra, Massimo Zeviani
Summary: Mitochondrial disorders are common inborn errors of metabolism, primarily due to dysfunction of the oxidative phosphorylation system (OXPHOS). Around half of diagnosed cases have a known genetic cause, often involving pathogenic variants in genes encoding structural subunits or factors directly involved in ETC assembly.
Review
Biochemistry & Molecular Biology
Margherita Protasoni, Massimo Zeviani
Summary: Mitochondria are intracellular organelles responsible for energy production in eukaryotic cells, with growing interest due to their association with various pathologies. Dysfunction of mitochondria can lead to a wide range of clinical phenotypes, particularly affecting tissues with high-energy demand. Mitochondrial diseases are genetically heterogeneous conditions, making it difficult to identify common causes and potential therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Erika Fernandez-Vizarra, Sandra Lopez-Calcerrada, Luke E. Formosa, Rafael Perez-Perez, Shujing Ding, Ian M. Fearnley, Joaquin Arenas, Miguel A. Martin, Massimo Zeviani, Michael T. Ryan, Cristina Ugalde
Summary: The study of mitochondrial respiratory chain function in relation to its structural organization is essential for understanding eukaryotic cell metabolism. The complexome profiling technique has provided valuable information on the composition and assembly of MRC complexes, including larger supercomplexes and respirasomes. SCAFI plays a role in connecting individual MRC complexes III and IV, but is not the main player in respirasome formation as previously thought.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2021)
Article
Cell Biology
Kristyna Cunatova, David Pajuelo Reguera, Marek Vrbacky, Erika Fernandez-Vizarra, Shujing Ding, Ian M. Fearnley, Massimo Zeviani, Josef Houstek, Tomas Mracek, Petr Pecina
Summary: The study reveals that in the OXPHOS system localized in the inner mitochondrial membrane, interconnected complexes form supercomplexes to maintain ATP production. Deficiencies in cytochrome c oxidase (cIV) or cytochrome bc1 complex (cIII) affect the formation and maintenance of NADH dehydrogenase (cI). Experimental evidence confirms the interdependency between cI and cIV.
Letter
Genetics & Heredity
Alessandra Torraco, Reza Maroofian, Agnes Rotig, Enrico Bertini, Daniele Ghezzi, Rosalba Carrozzo, Daria Diodato
Review
Biochemistry & Molecular Biology
Massimo Zeviani, Valerio Carelli
Summary: The retina is a vulnerable target for defects in oxidative phosphorylation (OXPHOS) due to mitochondrial impairment, resulting in conditions such as retinal dystrophy and optic atrophy. Mutations in mitochondrial DNA (mtDNA) and nuclear genes are implicated in mitochondrial retinopathies, presenting as isolated diseases or part of more complex syndromes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Massimo Zeviani, Carlo Viscomi
Summary: Mitochondria are vital organelles responsible for generating energy in cells. Mutations in mtDNA or nuclear genes can lead to complex neurological disorders. Understanding these diseases is essential for the field of mitochondrial medicine due to the diverse genetic and phenotypic heterogeneity.
Article
Genetics & Heredity
Vicente A. Yepez, Mirjana Gusic, Robert Kopajtich, Christian Mertes, Nicholas H. Smith, Charlotte L. Alston, Rui Ban, Skadi Beblo, Riccardo Berutti, Holger Blessing, Elzbieta Ciara, Felix Distelmaier, Peter Freisinger, Johannes Haeberle, Susan J. Hayflick, Maja Hempel, Yulia S. Itkis, Yoshihito Kishita, Thomas Klopstock, Tatiana D. Krylova, Costanza Lamperti, Dominic Lenz, Christine Makowski, Signe Mosegaard, Michaela F. Mueller, Gerard Munoz-Pujol, Agnieszka Nadel, Akira Ohtake, Yasushi Okazaki, Elena Procopio, Thomas Schwarzmayr, Joel Smet, Christian Staufner, Sarah L. Stenton, Tim M. Strom, Caterina Terrile, Frederic Tort, Rudy Van Coster, Arnaud Vanlander, Matias Wagner, Manting Xu, Fang Fang, Daniele Ghezzi, Johannes A. Mayr, Dorota Piekutowska-Abramczuk, Antonia Ribes, Agnes Roetig, Robert W. Taylor, Saskia B. Wortmann, Kei Murayama, Thomas Meitinger, Julien Gagneur, Holger Prokisch
Summary: The lack of functional evidence hampers variant interpretation, but further sequencing of transcriptomes can help probe gene expression defects. A streamlined experimental and computational process involving RNA-seq analysis of skin fibroblasts led to the establishment of genetic diagnoses for 16% of WES-inconclusive cases, with detection of aberrant gene expression playing a major role in diagnosis, especially in identifying splice-disrupting variants.
Article
Cell Biology
Alessia Nasca, Andrea Legati, Megi Meneri, Melisa Emel Ermert, Chiara Frascarelli, Nadia Zanetti, Manuela Garbellini, Giacomo Pietro Comi, Alessia Catania, Costanza Lamperti, Dario Ronchi, Daniele Ghezzi
Summary: This study reports the identification of biallelic ENDOG variants in a patient with progressive external ophthalmoplegia, mitochondrial myopathy, and multiple mtDNA deletions in muscle. The absence of the ENDOG protein and the presence of multiple mtDNA deletions indicate the pathogenicity of the identified variants. The accumulation of low-level heteroplasmic mtDNA point mutations suggests a possible role of ENDOG in mtDNA replication or repair.
Article
Biochemistry & Molecular Biology
Mirko Baglivo, Alessia Nasca, Eleonora Lamantea, Stefano Vinci, Manuela Spagnolo, Silvia Marchet, Holger Prokisch, Alessia Catania, Costanza Lamperti, Daniele Ghezzi
Summary: Leber's hereditary optic neuropathy (LHON) is a disease that causes visual loss due to damage to the optical nerve. In this study, the respiratory parameters of LHON patients' fibroblasts were evaluated, revealing reduced respiration in untreated conditions and no significant improvement after idebenone supplementation. The responsiveness of cultured cells to idebenone treatment did not fully reflect in vivo data, indicating the need for further evaluation of cellular respiration as a potential biomarker for LHON prognosis and treatment response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Federica Invernizzi, Rossella Izzo, Isabel Colangelo, Andrea Legati, Nadia Zanetti, Barbara Garavaglia, Eleonora Lamantea, Lorenzo Peverelli, Anna Ardissone, Isabella Moroni, Lorenzo Maggi, Silvia Bonanno, Laura Fiori, Daniele Velardo, Francesca Magri, Giacomo P. Comi, Dario Ronchi, Daniele Ghezzi, Costanza Lamperti
Summary: This study aimed to investigate the possible genetic causes of recurrent hyperCKemia or clinical suspicion of inherited metabolic myopathy. A cohort of 139 patients was analyzed and a genetic diagnosis was obtained in 15.1% of cases, while candidate variants or variants of uncertain significance were found in a further 39.5%. The results confirmed the high genetic heterogeneity of hyperCKemia and metabolic myopathies, suggesting the existence of additional genes associated with this condition and the possibility of cases being caused by extrinsic factors.
Article
Clinical Neurology
Alberto A. Zambon, Daniele Ghezzi, Cristina Baldoli, Gianni Cutillo, Katia Fontana, Valentina Sofia, Maria Grazia Patricelli, Alessia Nasca, Stefano Vinci, Ivana Spiga, Eleonora Lamantea, Giovanna F. Fanelli, Maria Grazia Natali Sora, Rosanna Rovelli, Antonella Poloniato, Paola Carrera, Massimo Filippi, Graziano Barera
Summary: This study presents a novel phenotype associated with AIFM1 and reviews the existing literature on AIFM1-related disorders. Through various tests and studies, a pathogenic variant in the AIFM1 gene was identified and its effects on cellular function were observed. The patient exhibited drug-resistant, electro-clinical, multifocal seizures shortly after birth, and brain MRI revealed brain swelling and signal alteration in specific areas. Functional studies on cultured fibroblasts showed a reduction in AIFM1 protein amount and defective activities of respiratory chain complexes.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)