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 a...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.
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...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.
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 me...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 O 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.
Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent chronic liver disease characterized by an elusive etiology. In its advanced stages, this condition can pose life-threatening implications. Mitochondr...Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent chronic liver disease characterized by an elusive etiology. In its advanced stages, this condition can pose life-threatening implications. Mitochondrial dysfunction due to its impact on hepatic lipid homeostasis, cytokine release, ROS production, and cell death, contributes to the pathogenesis of NAFLD. Previous research reveals a direct link between NAFLD genetic predictors and mitochondrial dysfunction. The emphasis on the D-loop stems from its association with impaired mtDNA replication, underscoring its crucial role in NAFLD progression. We included 38 Iranian NAFLD patients (comprising 16 patients with non-alcoholic fatty liver [NAFL] and 22 patients with non-alcoholic steatohepatitis [NASH]), with matched blood and liver tissue samples collected from each to compare variations in the mitochondrial D-loop sequence within samples. The mitochondrial DNA (mtDNA) D-loop region was amplified using PCR, and variations were identified through sequencing. The resultant sequences were compared with the reference sequence of human mtDNA available in the MITOMAP Database for comparative analysis. In this study, 97 somatic mutations in the mtDNA D-loop region were identified in NAFLD patients. Our study revealed significant difference between the NAFLD patients and control group in 13 detected mutations (P ≤ 0.05). Novel mutations were discovered in hepatic tissues, while mutation 16220-16221ins C was found in both tissues and blood. A significant difference was found in the distribution of D310 and mt514-mt523 (CA)n repeat variations between NAFLD patients and the control group (P < 0.001). C to T and T to C transitions were the prevalent substitution among patients. Identification of the 16220-16221ins C mutation in both blood and tissue samples from NAFLD patients holds substantial promise as a potential diagnostic marker. However, further research is imperative to corroborate these findings.
Recent studies revealed that mitochondria are not only a place of vitamin D metabolism but also direct or indirect targets of its activities. This review summarizes current knowledge on the regulation of ion channels fro...Recent studies revealed that mitochondria are not only a place of vitamin D 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 D (1,25(OH)D). 1,25(OH)D, 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)D deficiency induces ionic remodeling and 1,25(OH)D regulates the activity of multiple ion channels. There are two main theories on how 1,25(OH)D can modify the function of ion channels. First, describes the involvement of genomic pathways of response to 1,25(OH)D 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 D activities. It was shown, that 1,25(OH)D 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)D 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.
Polesel M, Wildschut MHE, Doucerain C
… +10 more, Kuhn M, Flace A, Sá Zanetti L, Steck AL, Wilhelm M, Ingles-Prieto A, Wiedmer T, Superti-Furga G, Manolova V, Dürrenberger F
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...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.
Telomere length (TL) and mitochondrial DNA copy number (mt-cn) are associated with embryonic development. Here, we investigated the correlation between TL and mt-cn in bovine embryos to determine whether TL regulates mt-...Telomere length (TL) and mitochondrial DNA copy number (mt-cn) are associated with embryonic development. Here, we investigated the correlation between TL and mt-cn in bovine embryos to determine whether TL regulates mt-cn. TL and mt-cn were closely correlated in embryos derived from six bulls. Treatment of embryos with a telomerase inhibitor (TMPyP) and siTERT shortened the TL and reduced mt-cn in blastocysts. RNA-sequencing of blastocysts developed with TMPyP revealed differentially expressed genes associated with transforming growth factor-β1 signaling and inflammation. In conclusion, TL regulates mt-cn in embryos.
Mitochondrion
· 2024 May · PMID 38663836
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Aging probably is the most complexed process in biology. It is manifested by a variety of hallmarks. These hallmarks weave a network of aging; however, each hallmark is not uniformly strong for the network. It is the wea...Aging probably is the most complexed process in biology. It is manifested by a variety of hallmarks. These hallmarks weave a network of aging; however, each hallmark is not uniformly strong for the network. It is the weakest link determining the strengthening of the network of aging, or the maximum lifespan of an organism. Therefore, only improvement of the weakest link has the chance to increase the maximum lifespan but not others. We hypothesize that mitochondrial dysfunction is the weakest link of the network of aging. It may origin from the innate intramitochondrial immunity related to the activities of pathogen DNA recognition receptors. These receptors recognize mtDNA as the PAMP or DAMP to initiate the immune or inflammatory reactions. Evidence has shown that several of these receptors including TLR9, cGAS and IFI16 can be translocated into mitochondria. The potentially intramitochondrial presented pathogen DNA recognition receptors have the capacity to attack the exposed second structures of the mtDNA during its transcriptional or especially the replicational processes, leading to the mtDNA mutation, deletion, heteroplasmy colonization, mitochondrial dysfunction, and alterations of other hallmarks, as well as aging. Pre-consumption of the intramitochondrial presented pathogen DNA recognition receptors by medical interventions including development of mitochondrial targeted small molecule which can neutralize these receptors may retard or even reverse the aging to significantly improve the maximum lifespan of the organisms.
Mitochondrion
· 2024 May · PMID 38643865
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Mitochondria are the membrane-bound organelles producing energy for cellular metabolic processes. They orchestrate diverse cell signaling cascades regulating cellular homeostasis. This functional versatility may be attri...Mitochondria are the membrane-bound organelles producing energy for cellular metabolic processes. They orchestrate diverse cell signaling cascades regulating cellular homeostasis. This functional versatility may be attributed to their ability to regulate mitochondrial dynamics, biogenesis, and apoptosis. The Hippo pathway, a conserved signaling pathway, regulates various cellular processes, including mitochondrial functions. Through its effectors YAP and TAZ, the Hippo pathway regulates transcription factors and creates a seriatim process that mediates cellular metabolism, mitochondrial dynamics, and survival. Mitochondrial dynamics also potentially regulates Hippo signaling activation, indicating a bidirectional relationship between the two. This review outlines the interplay between the Hippo signaling components and the multifaceted role of mitochondria in cellular homeostasis under physiological and pathological conditions.
Cerebral ischemic stroke is a major contributor to physical impairments and premature death worldwide. The available reperfusion therapies for stroke in the form of mechanical thrombectomy and intravenous thrombolysis in...Cerebral ischemic stroke is a major contributor to physical impairments and premature death worldwide. The available reperfusion therapies for stroke in the form of mechanical thrombectomy and intravenous thrombolysis increase the risk of cerebral ischemia-reperfusion (I-R) injury due to sudden restoration of blood supply to the ischemic region. The injury is manifested by hemorrhagic transformation, worsening of neurological impairments, cerebral edema, and progression to infarction in surviving patients. A complex network of multiple pathological processes has been known to be involved in the pathogenesis of I-R injury. Primarily, 3 major contributors namely oxidative stress, neuroinflammation, and mitochondrial failure have been well studied in I-R injury. A transcription factor, Nrf2 (Nuclear factor erythroid 2-related factor 2) plays a crucial defensive role in resisting the deleterious effects of I-R injury and potentiating the cellular protective mechanisms. In this review, we delve into the critical function of mitochondria and Nrf2 in the context of cerebral I-R injury. We summarized how oxidative stress, neuroinflammation, and mitochondrial anomaly contribute to the pathophysiology of I-R injury and further elaborated the role of Nrf2 as a pivotal guardian of cellular integrity. The review further highlighted Nrf2 as a putative therapeutic target for mitochondrial dysfunction in cerebral I-R injury management.
Welikala A, Desai S, Pratap Singh P
… +7 more, Fernando A, Thangaraj K, van Driem G, Adikari G, Tennekoon K, Chaubey G, Ranasinghe R
Mitochondrion
· 2024 May · PMID 38626841
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Linguistic data from South Asia identified several language isolates in the subcontinent. The Vedda, an indigenous population of Sri Lanka, are the least studied amongst them. Therefore, to understand the initial peoplin...Linguistic data from South Asia identified several language isolates in the subcontinent. The Vedda, an indigenous population of Sri Lanka, are the least studied amongst them. Therefore, to understand the initial peopling of Sri Lanka and the genetic affinity of the Vedda with other populations in Eurasia, we extensively studied the high-resolution autosomal and mitogenomes from the Vedda population of Sri Lanka. Our autosomal analyses suggest a close genetic link of Vedda with the tribal populations of India despite no evidence of close linguistic affinity, thus suggesting a deep genetic link of the Vedda with these populations. The mitogenomic analysis supports this association by pointing to an ancient link with Indian populations. We suggest that the Vedda population is a genetically drifted group with limited gene flow from neighbouring Sinhalese and Sri Lankan Tamil populations. Interestingly, the genetic ancestry sharing of Vedda neglects the isolation-by-distance model. Collectively, the demography of Sri Lanka is unique, where Sinhalese and Sri Lankan Tamil populations excessively admixed, whilst Vedda largely preserved their isolation and deep genetic association with India.
Mitochondrion
· 2024 May · PMID 38604460
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DEAD-box helicases are important players in mitochondrial gene expression, which is necessary for mitochondrial respiration. In this study, we characterized Schizosaccharomyces pombe Mss116 (spMss116), a member of the fa...DEAD-box helicases are important players in mitochondrial gene expression, which is necessary for mitochondrial respiration. In this study, we characterized Schizosaccharomyces pombe Mss116 (spMss116), a member of the family of DEAD-box RNA helicases. Deletion of spmss116 in a mitochondrial intron-containing background significantly reduced the levels of mitochondrial DNA (mtDNA)-encoded cox1 and cob1 mRNAs and impaired mitochondrial translation, leading to a severe respiratory defect and a loss of cell viability during stationary phase. Deletion of mitochondrial introns restored the levels of cox1 and cob1 mRNAs to wide-type (WT) levels but could not restore mitochondrial translation and respiration in Δspmss116 cells. Furthermore, deletion of spmss116 in both mitochondrial intron-containing and intronless backgrounds impaired mitoribosome assembly and destabilization of mitoribosomal proteins. Our findings suggest that defective mitochondrial translation caused by deletion of spmss116 is most likely due to impaired mitoribosome assembly.
Maliszewska-Olejniczak K, Pytlak K, Dabrowska A
… +6 more, Zochowska M, Hoser J, Lukasiak A, Zajac M, Kulawiak B, Bednarczyk P
Mitochondrion
· 2024 May · PMID 38604459
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Plasma membrane large-conductance calcium-activated potassium (BK) channels are important players in various physiological processes, including those mediated by epithelia. Like other cell types, human bronchial epitheli...Plasma membrane large-conductance calcium-activated potassium (BK) channels are important players in various physiological processes, including those mediated by epithelia. Like other cell types, human bronchial epithelial (HBE) cells also express BK in the inner mitochondrial membrane (mitoBK). The genetic relationships between these mitochondrial and plasma membrane channels and the precise role of mitoBK in epithelium physiology are still unclear. Here, we tested the hypothesis that the mitoBK channel is encoded by the same gene as the plasma membrane BK channel in HBE cells. We also examined the impact of channel loss on the basic function of HBE cells, which is to create a tight barrier. For this purpose, we used CRISPR/Cas9 technology in 16HBE14o- cells to disrupt the KCNMA1 gene, which encodes the α-subunit responsible for forming the pore of the plasma membrane BK channel. Electrophysiological experiments demonstrated that the disruption of the KCNMA1 gene resulted in the loss of BK-type channels in the plasma membrane and mitochondria. We have also shown that HBE ΔαBK cells exhibited a significant decrease in transepithelial electrical resistance which indicates a loss of tightness of the barrier created by these cells. We have also observed a decrease in mitochondrial respiration, which indicates a significant impairment of these organelles. In conclusion, our findings indicate that a single gene encodes both populations of the channel in HBE cells. Furthermore, this channel is critical for maintaining the proper function of epithelial cells as a cellular barrier.
Mitochondrion
· 2024 May · PMID 38599304
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Mitochondrial Ca uptake is essential in regulating bioenergetics, cell death, and cytosolic Ca transients. Mitochondrial Calcium Uniporter (MCU) mediates the mitochondrial Ca uptake. Though MCU regulation by MICUs is une...Mitochondrial Ca uptake is essential in regulating bioenergetics, cell death, and cytosolic Ca transients. Mitochondrial Calcium Uniporter (MCU) mediates the mitochondrial Ca uptake. Though MCU regulation by MICUs is unequivocally established, there needs to be more knowledge of whether divalent cations regulate MCU. Here, we set out to understand the mitochondrial matrix Mg-dependent regulation of MCU activity. We showed that decreased matrix [Mg] is associated with increased MCU activity and significantly prompted mitochondrial permeability transition pore opening. Our findings support the critical role of mMg in regulating MCU activity.
Bermejo-Guerrero L, Hernández-Voth A, Serrano-Lorenzo P
… +4 more, Blázquez A, Martin-Jimenez P, Martin MA, Domínguez-González C
Mitochondrion
· 2024 May · PMID 38599303
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OBJECTIVES: Thymidine kinase 2 deficiency (TK2d) is a rare autosomal recessive mitochondrial disorder. It manifests as a continuous clinical spectrum, from fatal infantile mitochondrial DNA depletion syndromes to adult-o...OBJECTIVES: Thymidine kinase 2 deficiency (TK2d) is a rare autosomal recessive mitochondrial disorder. It manifests as a continuous clinical spectrum, from fatal infantile mitochondrial DNA depletion syndromes to adult-onset mitochondrial myopathies characterized by ophthalmoplegia-plus phenotypes with early respiratory involvement. Treatment with pyrimidine nucleosides has recently shown striking effects on survival and motor outcomes in the more severe infantile-onset clinical forms. We present the response to treatment in a patient with adult-onset TK2d. METHODS: An adult with ptosis, ophthalmoplegia, facial, neck, and proximal muscle weakness, non-invasive nocturnal mechanical ventilation, and dysphagia due to biallelic pathogenic variants in TK2 received treatment with 260 mg/kg/day of deoxycytidine (dC) and deoxythymidine (dT) under a Compassionate Use Program. Prospective motor and respiratory assessments are presented. RESULTS: After 27 months of follow-up, the North Star Ambulatory Assessment improved by 11 points, he walked 195 m more in the 6 Minute-Walking-Test, ran 10 s faster in the 100-meter time velocity test, and the Forced Vital Capacity stabilized. Growth Differentiation Factor-15 (GDF15) levels, a biomarker of respiratory chain dysfunction, normalized. The only reported side effect was dose-dependent diarrhea. DISCUSSION: Treatment with dC and dT can significantly improve motor performance and stabilize respiratory function safely in patients with adult-onset TK2d.
Mitochondrion
· 2024 May · PMID 38599302
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Mitochondria are dynamic organelles that alter their morphological characteristics in response to functional needs. Therefore, mitochondrial morphology is an important indicator of mitochondrial function and cellular hea...Mitochondria are dynamic organelles that alter their morphological characteristics in response to functional needs. Therefore, mitochondrial morphology is an important indicator of mitochondrial function and cellular health. Reliable segmentation of mitochondrial networks in microscopy images is a crucial initial step for further quantitative evaluation of their morphology. However, 3D mitochondrial segmentation, especially in cells with complex network morphology, such as in highly polarized cells, remains challenging. To improve the quality of 3D segmentation of mitochondria in super-resolution microscopy images, we took a machine learning approach, using 3D Trainable Weka, an ImageJ plugin. We demonstrated that, compared with other commonly used methods, our approach segmented mitochondrial networks effectively, with improved accuracy in different polarized epithelial cell models, including differentiated human retinal pigment epithelial (RPE) cells. Furthermore, using several tools for quantitative analysis following segmentation, we revealed mitochondrial fragmentation in bafilomycin-treated RPE cells.
Mitochondrion
· 2024 May · PMID 38599301
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Ribosome biogenesis, involving processing/assembly of rRNAs and r-proteins is a vital process. In Saccharomyces cerevisiae mitochondria, ribosomal small subunit comprises 15S rRNA (15S). While the 15S 5'-end processing u...Ribosome biogenesis, involving processing/assembly of rRNAs and r-proteins is a vital process. In Saccharomyces cerevisiae mitochondria, ribosomal small subunit comprises 15S rRNA (15S). While the 15S 5'-end processing uses Ccm1p and Pet127p, the mechanisms of the 3'-end processing remain unclear. We reveal involvement of Rmd9p in safeguarding/processing 15S 3'-end. Rmd9p deficiency results in a cleavage at a position 183 nucleotides upstream of 15S 3'-end, and in the loss of the 3'-minor domain. Rmd9p binds to the sequences in the 3'-end region of 15S, and a genetic interaction between rmd9 and dss1 indicates that Rmd9p regulates/limits mtEXO activity during the 3'-end spacer processing.
Borriello G, Buonincontri V, de Donato A
… +7 more, Della Corte M, Gravina I, Iulianiello P, Joshi R, Mone P, Cacciola G, Viggiano D
Mitochondrion
· 2024 May · PMID 38599300
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Mitochondrial volume is maintained through the permeability of the inner mitochondrial membrane by a specific aquaporin and the osmotic balance between the mitochondrial matrix and cellular cytoplasm. Various electrolyte...Mitochondrial volume is maintained through the permeability of the inner mitochondrial membrane by a specific aquaporin and the osmotic balance between the mitochondrial matrix and cellular cytoplasm. Various electrolytes, such as calcium and hydrogen ions, potassium, and sodium, as well as other osmotic substances, affect the swelling of mitochondria. Intracellular glucose levels may also affect mitochondrial swelling, although the relationship between mitochondrial ion homeostasis and intracellular glucose is poorly understood. This article reviews what is currently known about how the Sodium-Glucose transporter (SGLT) may impact mitochondrial sodium (Na+) homeostasis. SGLTs regulate intracellular glucose and sodium levels and, therefore, interfere with mitochondrial ion homeostasis because mitochondrial Na+ is closely linked to cytoplasmic calcium and sodium dynamics. Recently, a large amount of data has been available on the effects of SGLT2 inhibitors on mitochondria in different cell types, including renal proximal tubule cells, endothelial cells, mesangial cells, podocytes, neuronal cells, and cardiac cells. The current evidence suggests that SGLT inhibitors (SGLTi) may affect mitochondrial dynamics regarding intracellular Sodium and hydrogen ions. Although the regulation of mitochondrial ion channels by SGLTs is still in its infancy, the evidence accumulated thus far of the effect of SGLTi on mitochondrial functions certainly will foster further research in this direction.
Mitochondrion
· 2024 May · PMID 38514017
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Since the discovery of membrane contact sites between ER and mitochondria called mitochondria-associated membranes (MAMs), several pieces of evidence identified their role in the regulation of different cellular processe...Since the discovery of membrane contact sites between ER and mitochondria called mitochondria-associated membranes (MAMs), several pieces of evidence identified their role in the regulation of different cellular processes such as Ca signalling, mitochondrial transport, and dynamics, ER stress, inflammation, glucose homeostasis, and autophagy. The integrity of these membranes was found to be essential for the maintenance of these cellular functions. Accumulating pieces of evidence suggest that MAMs serve as a platform for autophagosome formation. However, the alteration within MAMs structure is associated with the progression of neurodegenerative diseases. Dysregulated autophagy is a hallmark of neurodegeneration. Here, in this review, we highlight the present knowledge on MAMs, their structural composition, and their roles in different cellular functions. We also discuss the association of MAMs proteins with impaired autophagy and their involvement in the progression of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.
Promila L, Joshi A, Khan S
… +2 more, Aggarwal A, Lahiri A
Mitochondrion
· 2023 Nov · PMID 38506094
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Rheumatoid arthritis (RA) is a chronic, autoimmune, and inflammatory disease that primarily targets the joints, leading to cartilage and bone destruction.Fibroblast-like synoviocytes (FLS) are specialized cells of the sy...Rheumatoid arthritis (RA) is a chronic, autoimmune, and inflammatory disease that primarily targets the joints, leading to cartilage and bone destruction.Fibroblast-like synoviocytes (FLS) are specialized cells of the synovial lining in the joint that plays a fundamental role in the development of RA. Particularly, FLS of RA patients (RA-FLS) in the joint exhibit specific characteristics like higher invading and immunogenic properties, hyperproliferation, and reduced apoptotic capacity, suggesting a dysfunctional mitochondrial pool in these cells. Mitochondria are emerging as a potential organelle that can decide cellular immunometabolism, invasion properties, and cell death. Accordingly, multiplestudies established that mitochondria are crucial in establishing RA. However, the underlying mechanism of impaired mitochondrial function in RA remains poorly understood. This review will provide an overview of the mitochondrial role in the progression of RA, specifically in the context of FLS biology. We will also outline how mitochondria-centric therapeutics can be achieved that would yield novel avenues of research in pathological mediation and prevention.