Mitochondrion[JOURNAL]
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200 papers
Mitochondrial bioenergetics of breast cancer.
Singh T, Sharma K, Jena L … +3 more , Kaur P, Singh S, Munshi A
Mitochondrion · 2024 Nov · PMID 39218051 · Publisher ↗
Breast cancer cells exhibit metabolic heterogeneity based on tumour aggressiveness. Glycolysis and mitochondrial respiration are two major metabolic pathways for ATP production. The oxygen flux, oxygen tension, proton le...
Breast cancer cells exhibit metabolic heterogeneity based on tumour aggressiveness. Glycolysis and mitochondrial respiration are two major metabolic pathways for ATP production. The oxygen flux, oxygen tension, proton leakage, protonmotive force, inner mitochondrial membrane potential, ECAR and electrochemical proton gradient maintain metabolic homeostasis, ATP production, ROS generation, heat dissipation, and carbon flow and are referred to as "sub-domains" of mitochondrial bioenergetics. Tumour aggressiveness is influenced by these mechanisms, especially when breast cancer cells undergo metastasis. These physiological parameters for healthy mitochondria are as crucial as energy demands for tumour growth and metastasis. The instant energy demands are already elucidated under Warburg effects, while these parameters may have dual functionality to maintain cellular bioenergetics and cellular health. The tumour cell might maintain these mitochondrial parameters for mitochondrial health or avoid apoptosis, while energy production could be a second priority. This review focuses explicitly on the crosstalk between metabolic domains and the utilisation of these parameters by breast cancer cells for their progression. Some major interventions are discussed based on mitochondrial bioenergetics that need further investigation. This review highlights the pathophysiological significance of mitochondrial bioenergetics and the regulation of its sub-domains by breast tumour cells for uncontrolled proliferation.
Glutathione inhibits lung cancer development by reducing interleukin-6 expression and reversing the Warburg effect.
Fan C, Chen G, Reiter RJ … +3 more , Bai Y, Zheng T, Fan L
Mitochondrion · 2024 Nov · PMID 39214486 · Publisher ↗
Reduced glutathione (GSH) is widely used as an antioxidant in clinical practice, but whether GSH affects the development of early lung cancer remains unclear. Herein, we investigated the mechanism underlying the anticanc...
Reduced glutathione (GSH) is widely used as an antioxidant in clinical practice, but whether GSH affects the development of early lung cancer remains unclear. Herein, we investigated the mechanism underlying the anticancer effect of GSH in patients with pulmonary nodules. Thirty patients with pulmonary nodules were treated with GSH intravenously for 10 days at a dose of 1.8 g/d, followed by oral administration of the drug at a dose of 0.4 g three times daily for 6 months. The results showed that GSH treatment promoted nodule absorption and reduced the IL-6 level in the peripheral blood of the patients. GSH reduced IL-6 expression in inflammatory BEAS-2B and lung cancer cells and inhibited the proliferation of lung cancer cell lines in vitro. In addition, GSH reduced IL-6 expression by decreasing ROS via down-regulating PI3K/AKT/FoxO pathways. Finally, GSH reversed the Warburg effect, restored mitochondrial function, and reduced the IL-6 expression via PI3K/AKT/FoxO pathways. The in vivo experiment confirmed that GSH inhibited lung cancer growth, improved mitochondrial function, and reduced the IL-6 expression by regulating key enzymes via the PI3K/AKT/FoxO pathway. In conclusion, we uncovered that GSH exerts an unprecedentedly potent anti-cancer effect to prevent the transformation of lung nodules to lung cancer by improving the mitochondrial function and suppressing inflammation via PI3K/AKT/FoxO pathway. This investigation innovatively positions GSH as a potentially safe and efficacious old drug with new uses, inhibiting inflammation and early lung cancer. The use of the drug offers a promising preventive strategy when administered during the early stages of lung cancer.
Associations of mitochondrial genomic variation with successful neurological aging.
Tamvaka N, Heckman MG, Johnson PW … +10 more , Soto-Beasley AI, Walton RL, Koga S, Uitti RJ, Parfitt F, Graff-Radford MR, Wszolek ZK, Graff-Radford N, Valentino RR, Ross OA
Mitochondrion · 2024 Sep · PMID 39179138 · Publisher ↗
Mitochondrial health is an integral factor in aging, with mitochondrial dysfunction known to increase with age and contribute to the development of age-related neurodegenerative disorders. Additionally, the mitochondrial...
Mitochondrial health is an integral factor in aging, with mitochondrial dysfunction known to increase with age and contribute to the development of age-related neurodegenerative disorders. Additionally, the mitochondrial genome (mtDNA) has been shown to acquire potentially damaging somatic variation as part of the aging process, while mtDNA single nucleotide polymorphism (SNPs) have been shown to be both protective and detrimental for various neurodegenerative diseases. Yet, little is known about the involvement of mtDNA variation in longevity and successful neurological aging. In this study, we examined the association of mtDNA SNPs, in the form of mitochondrial haplogroups, with successful neurological aging in 1,405 unrelated neurologically healthy subjects. Although not quite significant after correcting for multiple testing (P < 0.0017 considered as significant), we detected a nominally significant association between the I haplogroup (N = 45, 3.2 %) and a younger age (β: -5.00, P = 0.006), indicating that this haplogroup is observed less frequently in older neurologically healthy individuals and may be associated with decreased survival. Replication of this finding in independent neurologically healthy cohorts will be imperative for shaping our understanding of the biological processes underlying healthy neurological aging.
Activation of multifunctional DNA repair APE1/Ref-1 enzyme by the dietary phytochemical Ferulic acid protects human neuroblastoma SH-SY5Y cells against Aβ(25-35)-induced oxidative stress and inflammatory responses.
Kaur S, Verma H, Dhiman M … +1 more , Mantha AK
Mitochondrion · 2024 Nov · PMID 39151817 · Publisher ↗
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder associated with the amyloid beta (Aβ) and tau hallmarks. The molecular insights into how neuroinflammation is initially triggered and how it affects...
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder associated with the amyloid beta (Aβ) and tau hallmarks. The molecular insights into how neuroinflammation is initially triggered and how it affects neuronal cells are yet at the age of infancy. In this study, SH-SY5Y cells were used as a model for neurons by differentiating and were co-cultured with differentiated THP1 cells (microglia model) as well as treated with Aβ(25-35) and with antioxidant FA to study inflammatory, oxidative stress responses and their effects on co-cultured neurons. Neurons co-cultured with microglial cells showed pronounced increase in ROS levels, NOS expression, truncated N-terminal form (34 kDa) of APE1 expression and AIF's translocation in the nucleus. The pre-treatment of FA, on the other hand reversed these effects. It was further evaluated how FA/Aβ treatment altered microglial phenotype that in turn affected the neurons. Microglial cells showed M1 phenotype upon Aβ(25-35) stress, while FA induced M2 phenotype against Aβ stress, suggesting that FA alleviated Aβ induced phenotype and its associated effects in the co-cultured neurons by altering the phenotype of microglial cells and induced expression of full length (37 kDa) APE1 enzyme and inhibiting AIF's nuclear translocation, thus inhibiting apoptosis. This is the first study that revealed Aβ induced cleavage of APE1 enzyme in differentiated neurons, suggesting that APE1 may be the potential early target of Aβ that loses its function and exacerbates AD pathology. FA activated a fully functional form of APE1 against Aβ stress. The impaired function of APE1 could be the initial mechanism by which Aβ induces oxidative and inflammatory responses and dietary phytochemical FA can be a potential therapeutic strategy in managing the disease by activating APE1 that not only repairs oxidative DNA base damage but also maintains mitochondrial function and alleviates neuroinflammatory responses.
PKD regulates mitophagy to prevent oxidative stress and mitochondrial dysfunction during mouse oocyte maturation.
Liu YP, He B, Wang WX … +5 more , Pan WL, Jiao L, Yan JJ, Sun SC, Zhang Y
Mitochondrion · 2024 Sep · PMID 39147088 · Publisher ↗
Mitochondria play dominant roles in various cellular processes such as energy production, apoptosis, calcium homeostasis, and oxidation-reduction balance. Maintaining mitochondrial quality through mitophagy is essential,...
Mitochondria play dominant roles in various cellular processes such as energy production, apoptosis, calcium homeostasis, and oxidation-reduction balance. Maintaining mitochondrial quality through mitophagy is essential, especially as its impairment leads to the accumulation of dysfunctional mitochondria in aging oocytes. Our previous research revealed that PKD expression decreases in aging oocytes, and its inhibition negatively impacts oocyte quality. Given PKD's role in autophagy mechanisms, this study investigates whether PKD regulates mitophagy to maintain mitochondrial function and support oocyte maturation. When fully grown oocytes were treated with CID755673, a potent PKD inhibitor, we observed meiosis arrest at the metaphase I stage, along with decreased spindle stability. Our results demonstrate an association with mitochondrial dysfunction, including reduced ATP production and fluctuations in Ca homeostasis, which ultimately lead to increased ROS accumulation, stimulating oxidative stress-induced apoptosis and DNA damage. Further research has revealed that these phenomena result from PKD inhibition, which affects the phosphorylation of ULK, thereby reducing autophagy levels. Additionally, PKD inhibition leads to decreased Parkin expression, which directly and negatively affects mitophagy. These defects result in the accumulation of damaged mitochondria in oocytes, which is the primary cause of mitochondrial dysfunction. Taken together, these findings suggest that PKD regulates mitophagy to support mitochondrial function and mouse oocyte maturation, offering insights into potential targets for improving oocyte quality and addressing mitochondrial-related diseases in aging females.
Cyt b gene as a valid molecular authentication marker of cow leathers.
Pavithra N, Chris Felshia S, John Sundar V … +1 more , Gnanamani A
Mitochondrion · 2024 Sep · PMID 39134109 · Publisher ↗
Authentication of true (genuine) cow leathers is in high demand to promote merchandise and economic growth. The present study employs RT-PCR-based TaqMan assay to facilitate the identification. Species-specific primers a...
Authentication of true (genuine) cow leathers is in high demand to promote merchandise and economic growth. The present study employs RT-PCR-based TaqMan assay to facilitate the identification. Species-specific primers and probes were designed utilizing the existing NCBI data on mitochondrial DNA (mtDNA) genes, particularly the cytochrome b region (Cyt b). Mitochondrial DNA extracted from leather samples of both Bos taurus and Bos indicus and analyzed following the appropriate procedures. The RT-PCR results showed the designed primers and probes are exceptionally precise for cow leather samples. The established detection limit for the assay is estimated as 0.1 ng of DNA. In summary, the amplifiable mtDNA extracted from finished leather enables the identification of authentic cow leathers using the RT-PCR TaqMan assay, representing a pioneering report in this field.
Secondary mitochondrial dysfunction across the spectrum of hereditary and acquired muscle disorders.
Mak G, Tarnopolsky M, Lu JQ
Mitochondrion · 2024 Sep · PMID 39134108 · Publisher ↗
Mitochondria form a dynamic network within skeletal muscle. This network is not only responsible for producing adenosine triphosphate (ATP) through oxidative phosphorylation, but also responds through fission, fusion and...
Mitochondria form a dynamic network within skeletal muscle. This network is not only responsible for producing adenosine triphosphate (ATP) through oxidative phosphorylation, but also responds through fission, fusion and mitophagy to various factors, such as increased energy demands, oxidative stress, inflammation, and calcium dysregulation. Mitochondrial dysfunction in skeletal muscle not only occurs in primary mitochondrial myopathies, but also other hereditary and acquired myopathies. As such, this review attempts to highlight the clinical and histopathologic aspects of mitochondrial dysfunction seen in hereditary and acquired myopathies, as well as discuss potential mechanisms leading to mitochondrial dysfunction and therapies to restore mitochondrial function.
Coupling of β-adrenergic and Hippo pathway signaling: Implications for heart failure pathophysiology and metabolic therapy.
Du XJ, She G, Wu W … +1 more , Deng XL
Mitochondrion · 2024 Sep · PMID 39122227 · Publisher ↗
Activation of the sympatho-β-adrenergic receptor (βAR) system is the hallmark of heart disease with adverse consequences that facilitate the onset and progression of heart failure (HF). Use of β-blocking drugs has become...
Activation of the sympatho-β-adrenergic receptor (βAR) system is the hallmark of heart disease with adverse consequences that facilitate the onset and progression of heart failure (HF). Use of β-blocking drugs has become the front-line therapy for HF. Last decade has witnessed progress in research demonstrating a pivotal role of Hippo pathway in cardiomyopathy and HF. Clinical studies have revealed myocardial Hippo pathway activation/YAP-TEAD1 inactivation in several types of human cardiomyopathy. Experimental activation of cardiac Hippo signaling or inhibition of YAP-TEAD1 have been shown to leads dilated cardiomyopathy with severe mitochondrial dysfunction and metabolic reprogramming. Studies have also convincingly shown that stimulation of βAR activates cardiac Hippo pathway with inactivation of the down-stream effector molecules YAP/TAZ. There is strong evidence for the adverse consequences of the βAR-Hippo signaling leading to HF. In addition to promoting cardiomyocyte death and fibrosis, recent progress is the demonstration of mitochondrial dysfunction and metabolic reprogramming mediated by βAR-Hippo pathway signaling. Activation of cardiac βAR-Hippo signaling is potent in downregulating a range of mitochondrial and metabolic genes, whereas expression of pro-inflammatory and pro-fibrotic factors are upregulated. Coupling of βAR-Hippo pathway signaling is mediated by several kinases, mechanotransduction and/or Ca signaling, and can be blocked by β-antagonists. Demonstration of the converge of βAR signaling and Hippo pathway bears implications for a better understanding on the role of enhanced sympathetic nervous activity, efficacy of β-antagonists, and metabolic therapy targeting this pathway in HF. In this review we summarize the progress and discuss future research directions in this field.
Understanding the molecular basis of anti-fibrotic potential of intranasal curcumin and its association with mitochondrial homeostasis in silica-exposed mice.
Kumari S, Singh P, Dash D … +1 more , Singh R
Mitochondrion · 2024 Sep · PMID 39122226 · Publisher ↗
Silicosis is an occupational disease of the lungs brought in by repeated silica dust exposures. Inhalation of crystalline silica leads to persistent lung inflammation characterized by lung lesions due to granuloma format...
Silicosis is an occupational disease of the lungs brought in by repeated silica dust exposures. Inhalation of crystalline silica leads to persistent lung inflammation characterized by lung lesions due to granuloma formation. The specific molecular mechanism has not yet been identified, though. The Present study investigated the impact of silica-exposed lung fibrosis and probable molecular mechanisms. Here, Curcumin, derived from Curcuma longa shown to be an effective anti-inflammatory and anti-fibrotic molecule has been taken to investigate its therapeutic efficacy in silica-induced lung fibrosis. An experimental model of silicosis was established in mice where curcumin was administered an hour before intranasal silica exposure every alternate day for 35 days. Intranasal Curcumin treatment reduced silica-induced oxidative stress, inflammation marked by inflammatory cell recruitment, and prominent granuloma nodules along with aberrant collagen repair. Its protective benefits were confirmed by reduced MMP9 activities along with EMT markers (Vimentin and α-SMA). It has restored autophagy and suppressed the deposition of damaged mitochondria after silica exposure. Intranasal Curcumin also inhibited oxidative stress by boosting antioxidant enzyme activities and enhanced Nrf2-Keap1 expressions. Higher levels of PINK1, PARKIN, Cyt-c, P62/SQSTM, and damaged mitochondria in the silicosis group were significantly lowered after curcumin and dexamethasone treatments. Curcumin-induced autophagy resulted in reduced silica-induced mitochondria-dependent apoptosis. We report that intranasal curcumin treatment showed protective properties on pathological features prompted by silica particles, suggesting that the compound may constitute a promising strategy for the treatment of silicosis in the near future.
The Interplay of Mitochondrial Dysfunction in Oral Diseases: Recent Updates in Pathogenesis and Therapeutic Implications.
Soliman Wadan AH, Abdelsattar Ahmed M, Hussein Ahmed A … +3 more , El-Sayed Ellakwa D, Hamed Elmoghazy N, Gawish A
Mitochondrion · 2024 Sep · PMID 39111357 · Publisher ↗
Mitochondrial dysfunction is linked to various systemic and localized diseases, including oral diseases like periodontitis, oral cancer, and temporomandibular joint disorders. This paper explores the intricate mechanisms...
Mitochondrial dysfunction is linked to various systemic and localized diseases, including oral diseases like periodontitis, oral cancer, and temporomandibular joint disorders. This paper explores the intricate mechanisms underlying mitochondrial dysfunction in oral pathologies, encompassing oxidative stress, inflammation, and impaired energy metabolism. Furthermore, it elucidates the bidirectional relationship between mitochondrial dysfunction and oral diseases, wherein the compromised mitochondrial function exacerbates disease progression, while oral pathologies, in turn, exacerbate mitochondrial dysfunction. Understanding these intricate interactions offers insights into novel therapeutic strategies targeting mitochondrial function for managing oral diseases. This paper pertains to the mechanisms underlying mitochondrial dysfunction, its implications in various oral pathological and inflammatory conditions, and emerging versatile treatment approaches. It reviews current therapeutic strategies to mitigate mitochondrial dysfunction, including antioxidants, mitochondrial-targeted agents, and metabolic modulators.
Transplanting mitochondria from gastric epithelial cells reduces the malignancy of gastric cancer.
Kuo FC, Chen PC, You SY … +6 more , Tsai CC, Tsai HY, Liu CJ, Wu DC, Lin MW, Huang B
Mitochondrion · 2024 Sep · PMID 39067839 · Publisher ↗
Mitochondria are essential for energy supplementation and metabolic homeostasis of cancer cells. Using mitochondria transplantation to reduce the malignancy of gastric cancer (GC) cells is herein proposed. In our study n...
Mitochondria are essential for energy supplementation and metabolic homeostasis of cancer cells. Using mitochondria transplantation to reduce the malignancy of gastric cancer (GC) cells is herein proposed. In our study normal human gastric mucous epithelium cell line (GES-1) showed a lower mitochondrial membrane potential (MMP) compared to immortalized human vascular endothelial cell line (EAhy 926) and human gastric adenocarcinoma cell line (AGS). The transplantation of GES-1 mitochondria to AGS were confirmed both by confocal microscopy and flow cytometry. After transplanting GES-1 mitochondria, the AGS showed a reduced cell migration, and invasion without affecting cell viability and apoptosis. Investigating the expression of proteins involved in epithelial-mesenchymal-transition (EMT), transplanted GES-1 mitochondria reduced the expression of mesenchymal markers α-SMA, MMP-9, snail, vimentin and N-cadherin, whereas the epithelial markers E-cadherin and clauding-1 were not changed. The proteins implicated in the cell cycle such as cyclin B1 and D1 were decreased. In mice, inoculation with AGS carrying the transplanted GES-1 mitochondria resulted in smaller sized tumors. Further investigating the mitochondrial balance, the transplanted GES-1 mitochondria were more stably preserved compared to endogenous AGS mitochondria. The MMP, ATP production and mitochondrial mass decreased in GES-1 mitochondria and the mitophagic proteins LC3 II and PINK1 were up-regulated. In conclusion the decreased malignancy of AGS was a result of exogenous GES-1 mitochondria transplantation. This suggests for a therapy with low efficiency mitochondria transplantation in the treatment of cancer cells.
Early cardiac mechanics abnormalities in patients with mitochondrial diseases.
Lillo R, Meucci MC, Malara S … +8 more , Primiano G, Servidei S, Lombardo A, Grandinetti M, Massetti M, Lanza GA, Limongelli G, Graziani F
Mitochondrion · 2024 Sep · PMID 39047899 · Publisher ↗
BACKGROUND: Evidence about early cardiac mechanics abnormalities in patients with mitochondrial diseases (MDs) before overt cardiomyopathy is limited. METHODS: In this prospective study, we performed a comparative analys...
BACKGROUND: Evidence about early cardiac mechanics abnormalities in patients with mitochondrial diseases (MDs) before overt cardiomyopathy is limited. METHODS: In this prospective study, we performed a comparative analysis of conventional and speckle tracking echocardiographic parameters between patients with genetically identified MDs and no overt cardiomyopathy vs controls matched for age, sex and cardiovascular risk factors. The Newcastle mitochondrial disease adult scale (NMDAS) was calculated, using a threshold of > 21 as indicator of high disease severity. RESULTS: We enrolled 24 MDs patients (50 % males, mean age 47.2 ± 14.3 years), the most prevalent mutation was the MT-TL1 m.3243A>G (37.5 %). In MDs patients all dimensional echocardiographic parameters were similar to controls. Conversely, albeit normal, Tissue Doppler septal systolic (p = 0.002) and early diastolic velocities (p = 0.016) were significantly lower and E/e' ratio was higher (p = 0.032) in MDs. Moreover, LV-GLS was significantly reduced in MDs as compared to their counterparties (20.2 ± 1.6 vs 22.6 ± 1.5, p < 0.001). Similarly, LA reservoir and conduit strain were significantly lower in MDs (31.7 ± 7.0 vs 35.9 ± 6.6, p = 0.038; 19.7 ± 5.6 vs 23.1 ± 6.0, p = 0.049 respectively), while LA contractile strain was similar between the two groups. Lower values of LV-GLS were observed in patients with NMDAS > 21 vs patients with NMDAS ≤ 21 (19.0 ± 1.2 vs 21.0 ± 1.3, p = 0.001). CONCLUSIONS: In patients with MDs and no overt cardiomyopathy Tissue Doppler and speckle tracking analysis unveil worse LV systolic and diastolic function indices as compared to controls. Reduced LV-GLS values were found especially in those with worse disease burden.
Disturbance in communication between mitochondrial redox processes and the AMPK/PGC-1α/SIRT-1 axis influences diverse organ symptoms in lupus-affected mice.
Akhil A, Bansal R, Ankita A … +3 more , Kaur H, Monika M, Bhatnagar A
Mitochondrion · 2024 Sep · PMID 39025320 · Publisher ↗
BACKGROUND: Mechanisms behind multiple organ involvement in lupus, is still an enigma for researchers. Mitochondrial dysfunction and oxidative stress are known to be important aspects in lupus etiology however, their rol...
BACKGROUND: Mechanisms behind multiple organ involvement in lupus, is still an enigma for researchers. Mitochondrial dysfunction and oxidative stress are known to be important aspects in lupus etiology however, their role in lupus organ manifestation is yet to be understood. The present study is based on the understanding of interplay between AMPK/PGC-1α/SIRT-1 axis, mitochondrial complexes, and anti-oxidants levels, which might be involved in lupus organ pathology. METHODOLOGY: Pristane-induced Balb/c mice lupus model (PIL) was utilised and evaluation of anti-oxidants, mitochondrial complexes, pro-inflammatory cytokines levels, biochemical parameters were performed by standard procedures. Tissues were studied by haematoxylin and eosin staining followed by immunohistochemistry. The AMPK/PGC-1α/SIRT-1 expression was analysed by using qPCR and flowcytometry. Analysis of reactive oxygen species (ROS) among WBCs was performed by using various dyes (DCFDA, Mitosox, JC-1) on flowcytometry. RESULT: Significant presence of immune complexes (Tissue sections), ANA (Serum), and pro-inflammatory cytokines (plasma), diminished anti-oxidants and altered biochemical parameters depict the altered pathology in PIL which was accompanied by dysregulated mitochondrial complex activity. Differential expression of the AMPK/PGC-1α/SIRT-1 axis was detected in tissue and correlation with mitochondrial and antioxidant activity emerged as negative in PIL group while positive in controls. Close association was observed between ROS, mitochondrial membrane potential, and AMPK/PGC-1α/SIRT-1 axis in WBCs. CONCLUSION: This study concludes that mitochondria play a dual role in lupus organ pathology, contributing to organ damage while also potentially protecting against damage through the regulation of interactions between antioxidants and the AMPK axis expression.
Screening clusters of charged residues in plants' mitochondrial proteins and biological significance.
Nebli S, Rebai A, Ayadi I
Mitochondrion · 2024 Sep · PMID 39013535 · Publisher ↗
Protein function is dependent on charge interactions and charge biased regions, which are involved in a wide range of cellular and biochemical processes. We report the development of a new algorithm implemented in Python...
Protein function is dependent on charge interactions and charge biased regions, which are involved in a wide range of cellular and biochemical processes. We report the development of a new algorithm implemented in Python and its use to identify charge clusters CC (NegativeCC: NCC, PositiveCC: PCC and MixedCC: MCC) and compare their presence in mitochondrial proteins of plant groups. To characterize the resulting CC, statistical, structural and functional analyses were conducted. The screening of 105 399 protein sequences showed that 2.6 %, 0.48 % and 0.03 % of the proteins contain NCC, PCC and MCC, respectively. Mitochondrial proteins encoded by the nuclear genome of green algae have the biggest proportion of both PCC (1.6 %) and MCC (0.4 %) and mitochondrial proteins coded by the nuclear genome of other plants group have the highest portion of NCC (7.5 %). The mapping of the identified CC showed that they are mainly located in the terminal regions of the protein. Annotation showed that proteins with CC are classified as binding proteins, are included in the transmembrane transport processes, and are mainly located in the membrane. The CC scanning revealed the presence of 2373 and 784 sites and 192 and 149 motif profiles within NCC and PCC, respectively. The investigation of CC within pentatricopeptide repeat-containing proteins revealed that they are involved in correct and specific RNA editing. CC were proven to play a key role in providing insightful structural and functional information of complex protein assemblies which could be useful in biotechnological applications.
Longitudinal changes in mitochondrial-associated measures and insulin resistance in youth with perinatally-acquired HIV in the U.S.
Gojanovich GS, Yu W, Zhang ZJ … +7 more , Jacobson DL, Yao TJ, Jao J, Libutti DE, Geffner ME, Gerschenson M, Pediatric HIV/AIDS Cohort Study
Mitochondrion · 2024 Sep · PMID 39009104 · Full text
HIV infection and its treatment are associated with mitochondrial dysfunction and metabolic derangement. However, longitudinal changes in oxidative phosphorylation activities [Complex I (C1) and Complex IV (C4)], or veno...
HIV infection and its treatment are associated with mitochondrial dysfunction and metabolic derangement. However, longitudinal changes in oxidative phosphorylation activities [Complex I (C1) and Complex IV (C4)], or venous lactate/pyruvate ratios (LPR), and their relationships with insulin resistance (IR), remain unclear in youth living with perinatally-acquired HIV (YPHIV). We measured venous LPR, C1, and C4 activities in blood cells and homeostatic model assessment for IR (HOMA-IR) over two years. Limited longitudinal differences in mitochondrial-related measures and IR were observed in YPHIV vs youth perinatally HIV-exposed but uninfected. There were no systematic differences in C1, C4, or HOMA-IR between the groups.
Iron chelation mitigates mitochondrial dysfunction and oxidative stress by enhancing nrf2-mediated antioxidant responses in the renal cortex of a murine model of type 2 diabetes.
Peña-Montes DJ, Huerta-Cervantes M, Riveros-Rosas H … +8 more , Manzo-Avalos S, Aguilera-Méndez A, Huerta M, Trujillo X, Cortés-Rojo C, Montoya-Pérez R, Salgado-Garciglia R, Saavedra-Molina A
Mitochondrion · 2024 Sep · PMID 39004262 · Publisher ↗
Renal iron overload is a common complication of diabetes that leads to oxidative stress and mitochondrial dysfunction in the kidneys. This study investigated the effects of iron chelation using deferiprone on mitochondri...
Renal iron overload is a common complication of diabetes that leads to oxidative stress and mitochondrial dysfunction in the kidneys. This study investigated the effects of iron chelation using deferiprone on mitochondrial dysfunction and oxidative stress in the renal cortex of a murine model of type 2 diabetes. Diabetic rats were treated with deferiprone (50 mg/kg BW) for 16 weeks. Our results show that iron chelation with deferiprone significantly increased the nuclear accumulation of Nrf2, a transcription factor that regulates the expression of antioxidant enzymes. This led to enhanced antioxidant capacity, reduced production of reactive oxygen species, and improved mitochondrial bioenergetic function in diabetic rats. However, chronic iron chelation led to altered mitochondrial respiration and increased oxidative stress in non-diabetic rats. In conclusion, our findings suggest that iron chelation with deferiprone protects mitochondrial bioenergetics and mitigates oxidative stress in the renal cortex, involving the NRF2 pathway in type 2 diabetes.
Extracellular vesicles as carriers for mitochondria: Biological functions and clinical applications.
Liao Z, Tong B, Ke W … +3 more , Yang C, Wu X, Lei M
Mitochondrion · 2024 Sep · PMID 39002687 · Publisher ↗
In recent years, research has increasingly focused on the biogenesis of extracellular vesicles (EVs) and the sorting mechanisms for their contents. Mitochondria can be selectively loaded into EVs, serving as a way to mai...
In recent years, research has increasingly focused on the biogenesis of extracellular vesicles (EVs) and the sorting mechanisms for their contents. Mitochondria can be selectively loaded into EVs, serving as a way to maintain cellular mitochondrial homeostasis. EV-mediated mitochondrial transfer has also been shown to greatly impact the function of target cells. Based on the mechanism of EV-mediated mitochondrial transfer, therapies can be developed to treat human diseases. This review summarizes the recent advances in the biogenesis and molecular composition of EVs. It also highlights the sorting and trafficking mechanisms of mitochondrial components into EVs. Furthermore, it explores the current role of EV-mediated mitochondrial transfer in the development of human diseases, as well as its diagnostic and therapeutic applications.
Role of mitophagy in pulmonary hypertension: Targeting the mechanism and pharmacological intervention.
Wan JJ, Yi J, Wang FY … +4 more , Li X, Zhang C, Song L, Dai AG
Mitochondrion · 2024 Sep · PMID 38992857 · Publisher ↗
Mitophagy, a crucial pathway in eukaryotic cells, selectively eliminates dysfunctional mitochondria, thereby maintaining cellular homeostasis via mitochondrial quality control. Pulmonary hypertension (PH) refers to a pat...
Mitophagy, a crucial pathway in eukaryotic cells, selectively eliminates dysfunctional mitochondria, thereby maintaining cellular homeostasis via mitochondrial quality control. Pulmonary hypertension (PH) refers to a pathological condition where pulmonary arterial pressure is abnormally elevated due to various reasons, and the underlying pathogenesis remains elusive. This article examines the molecular mechanisms underlying mitophagy, emphasizing its role in PH and the progress in elucidating related molecular signaling pathways. Additionally, it highlights current drug regulatory pathways, aiming to provide novel insights into the prevention and treatment of pulmonary hypertension.
Neuroprotective compounds alter the expression of genes coding for proteins related to mitochondrial function in activated microglia.
Serrano-Marín J, Valenzuela R, Delgado C … +4 more , Quijano A, Navarro G, Labandeira-García JL, Franco R
Mitochondrion · 2024 Sep · PMID 38992856 · Publisher ↗
A hallmark of neuroinflammatory disorders is mitochondrial dysfunction. Nevertheless, the transcriptional changes underlying this alteration are not well-defined. Microglia activation, a decrease in mitochondrion biogene...
A hallmark of neuroinflammatory disorders is mitochondrial dysfunction. Nevertheless, the transcriptional changes underlying this alteration are not well-defined. Microglia activation, a decrease in mitochondrion biogenesis and a subsequent alteration of the redox are common factors in diseases coursing with neuroinflammation. In the last two decades, components of the adenosinergic system have been proposed as potential therapeutic targets to combat neuroinflammation. In this research, we analyzed by RNAseq the gene expression in activated microglia treated with an adenosine A receptor antagonist, SCH 582561, and/or an A receptor agonist, 2-Cl-IB-MECA, since these receptors are deeply related to neurodegeneration and inflammation. The analysis was focused on genes related to inflammation and REDOX homeostasis. It was detected that in the three conditions (microglia treated with 2-Cl-IB-MECA, SCH 582561, and their combination) more than 40 % of the detected genes codified by the mitochondrial genome were differentially expressed (FDR < 0.05) (14/34, 16/34, and 13/34) respectively, being almost all of them (>85 %) upregulated in the microglia treated with adenosinergic compounds. Also, we analyzed the differential expression of genes related to mitochondrial function and oxidative stress codified by the nuclear genome. Additionally, we evaluated the oxygen consumption rate (OCR) of mitochondria in microglia treated with LPS and IFN-γ, both alone and in combination with adenosinergic compounds. The data showed an improvement in mitochondrial function with the antagonist of the adenosine A receptor, compared to the effects of pro-inflammatory stimulus, confirming a functional effect consistent with the RNAseq data.
Differentiation activates mitochondrial OPA1 processing in myoblast cell lines.
Kaur H, Carrillo O, Garcia I … +10 more , Ramos I, St Vallier S, De La Torre P, Lopez A, Keniry M, Bazan D, Elizondo J, Grishma KC, Ann MacMillan-Crow L, Gilkerson R
Mitochondrion · 2024 Sep · PMID 38986925 · Full text
Mitochondrial optic atrophy-1 (OPA1) plays key roles in adapting mitochondrial structure to bioenergetic function. When transmembrane potential across the inner membrane (Δψ) is intact, long (L-OPA1) isoforms shape the i...
Mitochondrial optic atrophy-1 (OPA1) plays key roles in adapting mitochondrial structure to bioenergetic function. When transmembrane potential across the inner membrane (Δψ) is intact, long (L-OPA1) isoforms shape the inner membrane through membrane fusion and the formation of cristal junctions. When Δψ is lost, however, OPA1 is cleaved to short, inactive S-OPA1 isoforms by the OMA1 metalloprotease, disrupting mitochondrial structure and priming cellular stress responses such as apoptosis. Previously, we demonstrated that L-OPA1 of H9c2 cardiomyoblasts is insensitive to loss of Δψ via challenge with the protonophore carbonyl cyanide chlorophenyl hydrazone (CCCP), but that CCCP-induced OPA1 processing is activated upon differentiation in media with low serum supplemented with all-trans retinoic acid (ATRA). Here, we show that this developmental induction of OPA1 processing in H9c2 cells is independent of ATRA; moreover, pretreatment of undifferentiated H9c2s with chloramphenicol (CAP), an inhibitor of mitochondrial protein synthesis, recapitulates the Δψ-sensitive OPA1 processing observed in differentiated H9c2s. L6.C11 and C2C12 myoblast lines display the same developmental and CAP-sensitive induction of OPA1 processing, demonstrating a general mechanism of OPA1 regulation in mammalian myoblast cell settings. Restoration of CCCP-induced OPA1 processing correlates with increased apoptotic sensitivity. Moreover, OPA1 knockdown indicates that intact OPA1 is necessary for effective myoblast differentiation. Taken together, our results indicate that a novel developmental mechanism acts to regulate OMA1-mediated OPA1 processing in myoblast cell lines, in which differentiation engages mitochondrial stress sensing.
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