Mitochondrion最新文献

{"title":"Cell-penetrating peptides with nanoparticles hybrid delivery vectors and their uptake pathways","authors":"Moataz Dowaidar","doi":"10.1016/j.mito.2024.101906","DOIUrl":"10.1016/j.mito.2024.101906","url":null,"abstract":"<div><p>Cell-penetrating peptides (CPPs) are molecules that improve the cellular uptake of various molecular payloads that do not easily traverse the cellular membrane. CPPs can be found in pharmaceutical and medical products. The vast majority of cell-penetrating chemicals that are discussed in published research are peptide based. The paper also delves into the various applications of hybrid vectors. Because CPPs are able to carry cargo across the cellular membrane, they are a viable candidate for use as a suitable carrier for a wide variety of cargoes, such as siRNA, nanoparticles, and others. In which we discuss the CPPs, their classification, uptake mechanisms, hybrid vector systems, nanoparticles and their uptake mechanisms, etc. Further in this paper, we discuss CPPs conjugated to Nanoparticles, Combining CPPs with lipids and polymeric Nanoparticles in A Conjugated System, CPPs conjugated to nanoparticles for therapeutic purposes, and potential therapeutic uses of CPPs as delivery molecules. Also discussed the preclinical and clinical use of CPPS, intracellular trafficking of nanoparticles, and activatable and bioconjugated CPPs.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"78 ","pages":"Article 101906"},"PeriodicalIF":4.4,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141140310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ACAD9 treatment with bezafibrate and nicotinamide riboside temporarily stabilizes cardiomyopathy and lactic acidosis","authors":"Johan L.K. Van Hove ,&nbsp;Marisa W. Friederich ,&nbsp;Daniella H. Hock ,&nbsp;David A. Stroud ,&nbsp;Nikeisha J. Caruana ,&nbsp;Uwe Christians ,&nbsp;Björn Schniedewind ,&nbsp;Cole R. Michel ,&nbsp;Richard Reisdorph ,&nbsp;Edwin D.J. Lopez Gonzalez ,&nbsp;Charles Brenner ,&nbsp;Tonia E. Donovan ,&nbsp;Jessica C. Lee ,&nbsp;Kathryn C. Chatfield ,&nbsp;Austin A. Larson ,&nbsp;Peter R. Baker II ,&nbsp;Shawn E. McCandless ,&nbsp;Meghan F. Moore Burk","doi":"10.1016/j.mito.2024.101905","DOIUrl":"10.1016/j.mito.2024.101905","url":null,"abstract":"<div><p>Pathogenic <em>ACAD9</em> variants cause complex I deficiency. Patients presenting in infancy unresponsive to riboflavin have high mortality. A six-month-old infant presented with riboflavin unresponsive lactic acidosis and life-threatening cardiomyopathy. Treatment with high dose bezafibrate and nicotinamide riboside resulted in marked clinical improvement including reduced lactate and NT-pro-brain type natriuretic peptide levels, with stabilized echocardiographic measures. After a long stable period, the child succumbed from cardiac failure with infection at 10.5 months. Therapy was well tolerated. Peak bezafibrate levels exceeded its EC₅₀. The clinical improvement with this treatment illustrates its potential, but weak PPAR agonist activity of bezafibrate limited its efficacy.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"78 ","pages":"Article 101905"},"PeriodicalIF":4.4,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141140945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chelating mitochondrial iron and copper: Recipes, pitfalls and promise","authors":"Lucie J. Lamačová,&nbsp;Jan Trnka","doi":"10.1016/j.mito.2024.101903","DOIUrl":"10.1016/j.mito.2024.101903","url":null,"abstract":"<div><p>Iron and copper chelation therapy plays a crucial role in treating conditions associated with metal overload, such as hemochromatosis or Wilson’s disease. However, conventional chelators face challenges in reaching the core of iron and copper metabolism – the mitochondria. Mitochondria-targeted chelators can specifically target and remove metal ions from mitochondria, showing promise in treating diseases linked to mitochondrial dysfunction, including neurodegenerative diseases and cancer. Additionally, they serve as specific mitochondrial metal sensors. However, designing these new molecules presents its own set of challenges. Depending on the chelator’s intended use to prevent or to promote redox cycling of the metals, the chelating moiety must possess different donor atoms and an optimal value of the electrode potential of the chelator–metal complex. Various targeting moieties can be employed for selective delivery into the mitochondria. This review also provides an overview of the current progress in the design of mitochondria-targeted chelators and their biological activity investigation.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"78 ","pages":"Article 101903"},"PeriodicalIF":4.4,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The tissue-specific nature of physiological zebrafish mitochondrial bioenergetics","authors":"Rafael David Souto de Azevedo ,&nbsp;Kivia Vanessa Gomes Falcão ,&nbsp;Sinara Monica Vitalino de Almeida ,&nbsp;Marlyete Chagas Araújo ,&nbsp;Reginaldo Correia Silva-Filho ,&nbsp;Maria Bernadete de Souza Maia ,&nbsp;Ian Porto Gurgel do Amaral ,&nbsp;Ana Catarina Rezende Leite ,&nbsp;Ranilson de Souza Bezerra","doi":"10.1016/j.mito.2024.101901","DOIUrl":"10.1016/j.mito.2024.101901","url":null,"abstract":"<div><p>Zebrafish are a powerful tool to study a myriad of experimental conditions, including mitochondrial bioenergetics. Considering that mitochondria are different in many aspects depending on the tissue evaluated, in the zebrafish model there is still a lack of this investigation. Especially for juvenile zebrafish. In the present study, we examined whether different tissues from zebrafish juveniles show mitochondrial density- and tissue-specificity comparing brain, liver, heart, and skeletal muscle (SM). The liver and brain complex IV showed the highest O₂ consumption of all ETC in all tissues (10x when compared to other respiratory complexes). The liver showed a higher potential for ROS generation. In this way, the brain and liver showed more susceptibility to O₂^<img>− generation when compared to other tissues. Regarding Ca²⁺ transport, the brain showed greater capacity for Ca²⁺ uptake and the liver presented low Ca²⁺ uptake capacity. The liver and brain were more susceptible to producing ^<img>NO. The enzymes SOD and Catalase showed high activity in the brain, whereas GPx showed higher activity in the liver and CS in the SM. TEM reveals, as expected, a physiological diverse mitochondrial morphology. The essential differences between zebrafish tissues investigated probably reflect how the mitochondria play a diverse role in systemic homeostasis. This feature may not be limited to normal metabolic functions but also to stress conditions. In summary, mitochondrial bioenergetics in zebrafish juvenile permeabilized tissues showed a tissue-specificity and a useful tool to investigate conditions of redox system imbalance, mainly in the liver and brain.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"77 ","pages":"Article 101901"},"PeriodicalIF":4.4,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ancestry affects the transcription of small mitochondrial RNAs in human lymphocytes","authors":"Andrea Pozzi","doi":"10.1016/j.mito.2024.101907","DOIUrl":"10.1016/j.mito.2024.101907","url":null,"abstract":"<div><p>Mitochondrial mutations have been linked to changes in phenotypes such as fertility or longevity, however, these changes have been often inconsistent across populations for unknown reasons. A hypothesis that could explain this inconsistency is that some still uncharacterized mitochondrial products are mediating the phenotypic changes across populations. It has been hypothesized that one such product could be the small RNAs encoded in the mitochondrial genome, thus this work will provide new evidence for their existence and function. By using data from the 1000 genome project and knowledge from previously characterized nuclear small RNAs, this study found that 10 small RNAs encoded in tRNA fragments are consistently expressed in 450 individuals from five different populations. Furthermore, this study demonstrated that the expression of some small mitochondrial RNAs is different in individuals of African ancestry, similar to what was observed before in nuclear and mitochondria mRNAs. Lastly, we investigate the causes behind these differences in expression, showing that at least one of the mt-tRFs might be regulated by TRMT10B. The analyses presented in this work further support the small mitochondrial RNAs as functional molecules, and their population-specific expression supports the hypothesis that they act as a mediator between the nucleus and mitochondria differently across populations.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"77 ","pages":"Article 101907"},"PeriodicalIF":4.4,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transplantation of astrocyte-derived mitochondria into injured astrocytes has a protective effect following stretch injury","authors":"Qiu-yuan Gong ,&nbsp;Wei Wang ,&nbsp;Lin Cai,&nbsp;Yao Jing,&nbsp;Dian-xu Yang,&nbsp;Fang Yuan,&nbsp;Heng-li Tian,&nbsp;Jun Ding ,&nbsp;Hao Chen ,&nbsp;Zhi-ming Xu","doi":"10.1016/j.mito.2024.101902","DOIUrl":"10.1016/j.mito.2024.101902","url":null,"abstract":"<div><p>Traumatic brain injury (TBI) is a global public-health problem. Astrocytes, and their mitochondria, are important factors in the pathogenesis of TBI-induced secondary injury. Mitochondria extracted from healthy tissues and then transplanted have shown promise in models of a variety of diseases. However, the effect on recipient astrocytes is unclear. Here, we isolated primary astrocytes from newborn C57BL/6 mice, one portion of which was used to isolate mitochondria, and another was subjected to stretch injury (SI) followed by transplantation of the isolated mitochondria. After incubation for 12 h, cell viability, mitochondrial dysfunction, calcium overload, redox stress, inflammatory response, and apoptosis were improved. Live-cell imaging showed that the transplanted mitochondria were incorporated into injured astrocytes and fused with their mitochondrial networks, which was in accordance with the changes in the expression levels of markers of mitochondrial dynamics. The astrocytic IKK/NF–κB pathway was decelerated whereas the AMPK/PGC-1α pathway was accelerated by transplantation. Together, these results indicate that exogenous mitochondria from untreated astrocytes can be incorporated into injured astrocytes and fuse with their mitochondrial networks, improving cell viability by ameliorating mitochondrial dysfunction, redox stress, calcium overload, and inflammation.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"78 ","pages":"Article 101902"},"PeriodicalIF":4.4,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1567724924000606/pdfft?md5=c4c483746826b3c96d4a0c00b2579afb&pid=1-s2.0-S1567724924000606-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifaceted role of dynamin-related protein 1 in cardiovascular disease: From mitochondrial fission to therapeutic interventions","authors":"Satinder Kaur ,&nbsp;Naina Khullar ,&nbsp;Umashanker Navik ,&nbsp;Anjana Bali ,&nbsp;Gurjit Kaur Bhatti ,&nbsp;Jasvinder Singh Bhatti","doi":"10.1016/j.mito.2024.101904","DOIUrl":"10.1016/j.mito.2024.101904","url":null,"abstract":"<div><p>Mitochondria are central to cellular energy production and metabolic regulation, particularly in cardiomyocytes. These organelles constantly undergo cycles of fusion and fission, orchestrated by key proteins like Dynamin-related Protein 1 (Drp-1). This review focuses on the intricate roles of Drp-1 in regulating mitochondrial dynamics, its implications in cardiovascular health, and particularly in myocardial infarction. Drp-1 is not merely a mediator of mitochondrial fission; it also plays pivotal roles in autophagy, mitophagy, apoptosis, and necrosis in cardiac cells. This multifaceted functionality is often modulated through various post-translational alterations, and Drp-1′s interaction with intracellular calcium (Ca2 + ) adds another layer of complexity. We also explore the pathological consequences of Drp-1 dysregulation, including increased reactive oxygen species (ROS) production and endothelial dysfunction. Furthermore, this review delves into the potential therapeutic interventions targeting Drp-1 to modulate mitochondrial dynamics and improve cardiovascular outcomes. We highlight recent findings on the interaction between Drp-1 and sirtuin-3 and suggest that understanding this interaction may open new avenues for therapeutically modulating endothelial cells, fibroblasts, and cardiomyocytes. As the cardiovascular system increasingly becomes the focal point of aging and chronic disease research, understanding the nuances of Drp-1′s functionality can lead to innovative therapeutic approaches.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"78 ","pages":"Article 101904"},"PeriodicalIF":4.4,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141033220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Choice of medium affects PBMC quantification, cell size, and downstream respiratory analysis","authors":"Ida Bager Christensen ,&nbsp;Lucas Ribas ,&nbsp;Maria Mosshammer ,&nbsp;Marie-Louise Abrahamsen ,&nbsp;Michael Kühl ,&nbsp;Steen Larsen ,&nbsp;Flemming Dela ,&nbsp;Linn Gillberg","doi":"10.1016/j.mito.2024.101890","DOIUrl":"10.1016/j.mito.2024.101890","url":null,"abstract":"<div><p>High-resolution respirometry (HRR) can assess peripheral blood mononuclear cell (PBMC) bioenergetics, but no standardized medium for PBMC preparation and HRR analysis exist. Here, we study the effect of four different media (MiR05, PBS, RPMI, Plasmax) on the count, size, and HRR (Oxygraph-O2k) of intact PBMCs. Remarkably, the cell count was 21 % higher when PBMCs were resuspended in MiR05 than in PBS or Plasmax, causing O₂ flux underestimation during HRR due to inherent adjustments. Moreover, smaller cell size and cell aggregation was observed in MiR05. Based on our findings, we propose that Plasmax, PBS or RPMI is more suitable than MiR05 for HRR of intact PBMCs. We provide oxygen solubility factors for Plasmax and PBS and encourage further optimization of a standardized HRR protocol for intact PBMCs.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"77 ","pages":"Article 101890"},"PeriodicalIF":4.4,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1567724924000485/pdfft?md5=cd72df97e46171e9279b9d46f78cc07e&pid=1-s2.0-S1567724924000485-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Image-based quantification of mitochondrial iron uptake via Mitoferrin-2","authors":"Marcello Polesel ,&nbsp;Mattheus H.E. Wildschut ,&nbsp;Cédric Doucerain ,&nbsp;Michael Kuhn ,&nbsp;Anna Flace ,&nbsp;Leandro Sá Zanetti ,&nbsp;Anna-Lena Steck ,&nbsp;Maria Wilhelm ,&nbsp;Alvaro Ingles-Prieto ,&nbsp;Tabea Wiedmer ,&nbsp;Giulio Superti-Furga ,&nbsp;Vania Manolova ,&nbsp;Franz Dürrenberger","doi":"10.1016/j.mito.2024.101889","DOIUrl":"10.1016/j.mito.2024.101889","url":null,"abstract":"<div><p>Iron is a trace element that is critical for most living organisms and plays a key role in a wide variety of metabolic processes. In the mitochondrion, iron is involved in producing iron-sulfur clusters and synthesis of heme and kept within physiological ranges by concerted activity of multiple molecules. Mitochondrial iron uptake is mediated by the solute carrier transporters Mitoferrin-1 (SLC25A37) and Mitoferrin-2 (SLC25A28). While Mitoferrin-1 is mainly involved in erythropoiesis, the cellular function of the ubiquitously expressed Mitoferrin-2 remains less well defined. Furthermore, Mitoferrin-2 is associated with several human diseases, including cancer, cardiovascular and metabolic diseases, hence representing a potential therapeutic target. Here, we developed a robust approach to quantify mitochondrial iron uptake mediated by Mitoferrin-2 in living cells. We utilize HEK293 cells with inducible expression of Mitoferrin-2 and measure iron-induced quenching of rhodamine B[(1,10-phenanthroline-5-yl)-aminocarbonyl]benzyl ester (RPA) fluorescence and validate this assay for medium-throughput screening. This assay may allow identification and characterization of Mitoferrin-2 modulators and could enable drug discovery for this target.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"78 ","pages":"Article 101889"},"PeriodicalIF":4.4,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1567724924000473/pdfft?md5=0348899a4579d3f76e860569bddfbb32&pid=1-s2.0-S1567724924000473-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic and non-genomic action of vitamin D on ion channels – Targeting mitochondria","authors":"A.M. Olszewska,&nbsp;M.A. Zmijewski","doi":"10.1016/j.mito.2024.101891","DOIUrl":"10.1016/j.mito.2024.101891","url":null,"abstract":"<div><p>Recent studies revealed that mitochondria are not only a place of vitamin D₃ metabolism but also direct or indirect targets of its activities. This review summarizes current knowledge on the regulation of ion channels from plasma and mitochondrial membranes by the active form of vitamin D₃ (1,25(OH)₂D₃). 1,25(OH)₂D₃, is a naturally occurring hormone with pleiotropic activities; implicated in the modulation of cell differentiation, and proliferation and in the prevention of various diseases, including cancer. Many experimental data indicate that 1,25(OH)₂D₃ deficiency induces ionic remodeling and 1,25(OH)₂D₃ regulates the activity of multiple ion channels. There are two main theories on how 1,25(OH)₂D₃ can modify the function of ion channels. First, describes the involvement of genomic pathways of response to 1,25(OH)₂D₃ in the regulation of the expression of the genes encoding channels, their auxiliary subunits, or additional regulators. Interestingly, intracellular ion channels, like mitochondrial, are encoded by the same genes as plasma membrane channels. Therefore, the comprehensive genomic regulation of the channels from these two different cellular compartments we analyzed using a bioinformatic approach. The second theory explores non-genomic pathways of vitamin D₃ activities. It was shown, that 1,25(OH)₂D₃ indirectly regulates enzymes that impact ion channels, change membrane physical properties, or directly bind to channel proteins. In this article, the involvement of genomic and non-genomic pathways regulated by 1,25(OH)₂D₃ in the modulation of the levels and activity of plasma membrane and mitochondrial ion channels was investigated by an extensive review of the literature and analysis of the transcriptomic data using bioinformatics.</p></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"77 ","pages":"Article 101891"},"PeriodicalIF":4.4,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1567724924000497/pdfft?md5=02b6521a886ce791de1e4b350f243779&pid=1-s2.0-S1567724924000497-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140850530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}