bims-nenemi Biomed News
on Neuroinflammation, neurodegeneration and mitochondria
Issue of 2024‒03‒10
sixteen papers selected by
Marco Tigano, Thomas Jefferson University
  1. Absence of both MGME1 and POLG EXO abolishes mtDNA whereas absence of either creates unique mtDNA duplications.
  2. Mitochondrial DNA marks multiple sclerosis.
  3. Mitochondrial metabolism in neural stem cells and implications for neurodevelopmental and neurodegenerative diseases.
  4. Aging-induced tRNAGlu-derived fragment impairs glutamate biosynthesis by targeting mitochondrial translation-dependent cristae organization.
  5. Two ancient membrane pores mediate mitochondrial-nucleus membrane contact sites.
  6. STING dependent BAX-IRF3 signaling results in apoptosis during late-stage Coxiella burnetii infection.
  7. Hallmark Molecular and Pathological Features of POLG Disease are Recapitulated in Cerebral Organoids.
  8. Kinase signalling adaptation supports dysfunctional mitochondria in disease.
  9. Integrated stress response signaling acts as a metabolic sensor in fat tissues to regulate oocyte maturation and ovulation.
  10. PR55α-controlled protein phosphatase 2A inhibits p16 expression and blocks cellular senescence induction by γ-irradiation.
  11. Mitochondrial DNA mutations in extremely preterm infants with bronchopulmonary dysplasia.
  12. NDUFS4 regulates cristae remodeling in diabetic kidney disease.
  13. Mitochondrial ATP generation is more proteome efficient than glycolysis.
  14. Mitochondrial fission enhances IL-6-induced metastatic potential in ovarian cancer via ERK1/2 activation.
  15. Association between ambient particulate matter exposure and mitochondrial DNA copy number: A systematic review and meta-analysis.
  16. Crosstalk between vault RNAs and innate immunity.
  1. J Biol Chem. 2024 Mar 01. pii: S0021-9258(24)01623-5. [Epub ahead of print] 107128
    Absence of both MGME1 and POLG EXO abolishes mtDNA whereas absence of either creates unique mtDNA duplications.
    Christian D Gonzalez, Nadee Nissanka, Derek Van Booven, Anthony J Griswold, Carlos T Moraes.
      Both POLG and MGME1 are needed for mitochondrial DNA (mtDNA) maintenance in animal cells. POLG, the primary replicative polymerase of the mitochondria, has an exonuclease activity (3'→5') that corrects for the misincorporation of bases. MGME1 serves as an exonuclease (5'→3'), producing ligatable DNA ends. Although both have a critical role in mtDNA replication and elimination of linear fragments, these mechanisms are still not fully understood. Using digital PCR to evaluate and compare mtDNA integrity, we show that Mgme1 knock out (Mgme1 KK) tissue mtDNA is more fragmented than POLG exonuclease deficient "Mutator" (Polg MM) or WT tissue. In addition, next generation sequencing of mutant hearts showed abundant duplications in/nearby the D-loop region and unique 100bp duplications evenly spaced throughout the genome only in Mgme1 KK hearts. However, despite these unique mtDNA features at steady-state, we observed a similar delay in the degradation of mtDNA after an induced double strand DNA break in both Mgme1 KK and Polg MM models. Lastly, we characterized double mutant (Polg MM/Mgme1 KK) cells and show that mtDNA cannot be maintained without at least one of these enzymatic activities. We propose a model for the generation of these genomic abnormalities which suggests a role for MGME1 outside of nascent mtDNA end ligation. Our results highlight the role of MGME1 in and outside of the D-loop region during replication, support the involvement of MGME1 in dsDNA degradation and demonstrate that POLG EXO and MGME1 can partially compensate for each other in maintaining mtDNA.
    DOI:  https://doi.org/10.1016/j.jbc.2024.107128
  2. Nat Rev Neurol. 2024 Mar 05.
    Mitochondrial DNA marks multiple sclerosis.
    Ian Fyfe.
      
    DOI:  https://doi.org/10.1038/s41582-024-00948-w
  3. J Transl Med. 2024 Mar 04. 22(1): 238
    Mitochondrial metabolism in neural stem cells and implications for neurodevelopmental and neurodegenerative diseases.
    C Garone, F De Giorgio, S Carli.
      Mitochondria are cytoplasmic organelles having a fundamental role in the regulation of neural stem cell (NSC) fate during neural development and maintenance.During embryonic and adult neurogenesis, NSCs undergo a metabolic switch from glycolytic to oxidative phosphorylation with a rise in mitochondrial DNA (mtDNA) content, changes in mitochondria shape and size, and a physiological augmentation of mitochondrial reactive oxygen species which together drive NSCs to proliferate and differentiate. Genetic and epigenetic modifications of proteins involved in cellular differentiation (Mechanistic Target of Rapamycin), proliferation (Wingless-type), and hypoxia (Mitogen-activated protein kinase)-and all connected by the common key regulatory factor Hypoxia Inducible Factor-1A-are deemed to be responsible for the metabolic shift and, consequently, NSC fate in physiological and pathological conditions.Both primary mitochondrial dysfunction due to mutations in nuclear DNA or mtDNA or secondary mitochondrial dysfunction in oxidative phosphorylation (OXPHOS) metabolism, mitochondrial dynamics, and organelle interplay pathways can contribute to the development of neurodevelopmental or progressive neurodegenerative disorders.This review analyses the physiology and pathology of neural development starting from the available in vitro and in vivo models and highlights the current knowledge concerning key mitochondrial pathways involved in this process.
    Keywords:  HIF-1A; Mitochondrial metabolism; Neurodegenerative disorders; Neuronal development; Stem cells; Wnt; mTOR
    DOI:  https://doi.org/10.1186/s12967-024-05041-w
  4. Cell Metab. 2024 Mar 01. pii: S1550-4131(24)00057-3. [Epub ahead of print]
    Aging-induced tRNAGlu-derived fragment impairs glutamate biosynthesis by targeting mitochondrial translation-dependent cristae organization.
    Dingfeng Li, Xinyi Gao, Xiaolin Ma, Ming Wang, Chuandong Cheng, Tian Xue, Feng Gao, Yong Shen, Juan Zhang, Qiang Liu.
      Mitochondrial cristae, infoldings of the mitochondrial inner membrane, undergo aberrant changes in their architecture with age. However, the underlying molecular mechanisms and their contribution to brain aging are largely elusive. Here, we observe an age-dependent accumulation of Glu-5'tsRNA-CTC, a transfer-RNA-derived small RNA (tsRNA), derived from nuclear-encoded tRNAGlu in the mitochondria of glutaminergic neurons. Mitochondrial Glu-5'tsRNA-CTC disrupts the binding of mt-tRNALeu and leucyl-tRNA synthetase2 (LaRs2), impairing mt-tRNALeu aminoacylation and mitochondria-encoded protein translation. Mitochondrial translation defects disrupt cristae organization, leading to damaged glutaminase (GLS)-dependent glutamate formation and reduced synaptosomal glutamate levels. Moreover, reduction of Glu-5'tsRNA-CTC protects aged brains from age-related defects in mitochondrial cristae organization, glutamate metabolism, synaptic structures, and memory. Thus, beyond illustrating a physiological role for normal mitochondrial cristae ultrastructure in maintaining glutamate levels, our study defines a pathological role for tsRNAs in brain aging and age-related memory decline.
    Keywords:  angiogenin; brain aging; cristae organization; glutamate metabolism; memory decline; mitochondria; mitochondrial translation; tRNA-derived small RNAs
    DOI:  https://doi.org/10.1016/j.cmet.2024.02.011
  5. J Cell Biol. 2024 Apr 01. pii: e202304075. [Epub ahead of print]223(4):
    Two ancient membrane pores mediate mitochondrial-nucleus membrane contact sites.
    Jana Ovciarikova, Shikha Shikha, Alice Lacombe, Flavie Courjol, Rosalind McCrone, Wasim Hussain, Andrew Maclean, Leandro Lemgruber, Erica S Martins-Duarte, Mathieu Gissot, Lilach Sheiner.
      Coordination between nucleus and mitochondria is essential for cell survival, and thus numerous communication routes have been established between these two organelles over eukaryotic cell evolution. One route for organelle communication is via membrane contact sites, functional appositions formed by molecular tethers. We describe a novel nuclear-mitochondrial membrane contact site in the protozoan Toxoplasma gondii. We have identified specific contacts occurring at the nuclear pore and demonstrated an interaction between components of the nuclear pore and the mitochondrial protein translocon, highlighting them as molecular tethers. Genetic disruption of the nuclear pore or the TOM translocon components, TgNup503 or TgTom40, respectively, result in contact site reduction, supporting their potential involvement in this tether. TgNup503 depletion further leads to specific mitochondrial morphology and functional defects, supporting a role for nuclear-mitochondrial contacts in mediating their communication. The discovery of a contact formed through interaction between two ancient mitochondrial and nuclear complexes sets the ground for better understanding of mitochondrial-nuclear crosstalk in eukaryotes.
    DOI:  https://doi.org/10.1083/jcb.202304075
  6. Cell Death Dis. 2024 Mar 08. 15(3): 195
    STING dependent BAX-IRF3 signaling results in apoptosis during late-stage Coxiella burnetii infection.
    Manish Chauhan, Chelsea A Osbron, Heather S Koehler, Alan G Goodman.
      STING (STimulator of Interferon Genes) is a cytosolic sensor for cyclic dinucleotides (CDNs) and initiates an innate immune response upon binding to CDNs. Coxiella burnetii is a Gram-negative obligate intracellular bacterium and the causative agent of the zoonotic disease Q fever. The ability of C. burnetii to inhibit host cell death is a critical factor in disease development. Previous studies have shown that C. burnetii inhibits host cell apoptosis at early stages of infection. However, during the late-stages of infection, there is host cell lysis resulting in the release of bacteria to infect bystander cells. Thus, we investigated the role of STING during late-stages of C. burnetii infection and examined STING's impact on host cell death. We show that the loss of STING results in higher bacterial loads and abrogates IFNβ and IL6 induction at 12 days post-infection. The absence of STING during C. burnetii infection significantly reduces apoptosis through decreased caspase-8 and -3 activation. During infection, STING activates IRF3 which interacts with BAX. BAX then translocates to the mitochondria, which is followed by mitochondrial membrane depolarization. This results in increased cytosolic mtDNA in a STING-dependent manner. The presence of increased cytosolic mtDNA results in greater cytosolic 2'-3' cGAMP, creating a positive feedback loop and leading to further increases in STING activation and its downstream signaling. Taken together, we show that STING signaling is critical for BAX-IRF3-mediated mitochondria-induced apoptosis during late-stage C. burnetii infection.
    DOI:  https://doi.org/10.1038/s41419-024-06573-1
  7. Adv Sci (Weinh). 2024 Mar 06. e2307136
    Hallmark Molecular and Pathological Features of POLG Disease are Recapitulated in Cerebral Organoids.
    Anbin Chen, Tsering Yangzom, Yu Hong, Bjørn Christian Lundberg, Gareth John Sullivan, Charalampos Tzoulis, Laurence A Bindoff, Kristina Xiao Liang.
      In this research, a 3D brain organoid model is developed to study POLG-related encephalopathy, a mitochondrial disease stemming from POLG mutations. Induced pluripotent stem cells (iPSCs) derived from patients with these mutations is utilized to generate cortical organoids, which exhibited typical features of the diseases with POLG mutations, such as altered morphology, neuronal loss, and mitochondiral DNA (mtDNA) depletion. Significant dysregulation is also identified in pathways crucial for neuronal development and function, alongside upregulated NOTCH and JAK-STAT signaling pathways. Metformin treatment ameliorated many of these abnormalities, except for the persistent affliction of inhibitory dopamine-glutamate (DA GLU) neurons. This novel model effectively mirrors both the molecular and pathological attributes of diseases with POLG mutations, providing a valuable tool for mechanistic understanding and therapeutic screening for POLG-related disorders and other conditions characterized by compromised neuronal mtDNA maintenance and complex I deficiency.
    Keywords:  POLG; cortical organoids; iPSC; mitochondrial function; neuron
    DOI:  https://doi.org/10.1002/advs.202307136
  8. Front Mol Biosci. 2024 ;11 1354682
    Kinase signalling adaptation supports dysfunctional mitochondria in disease.
    George L Skalka, Mina Tsakovska, Daniel J Murphy.
      Mitochondria form a critical control nexus which are essential for maintaining correct tissue homeostasis. An increasing number of studies have identified dysregulation of mitochondria as a driver in cancer. However, which pathways support and promote this adapted mitochondrial function? A key hallmark of cancer is perturbation of kinase signalling pathways. These pathways include mitogen activated protein kinases (MAPK), lipid secondary messenger networks, cyclic-AMP-activated (cAMP)/AMP-activated kinases (AMPK), and Ca2+/calmodulin-dependent protein kinase (CaMK) networks. These signalling pathways have multiple substrates which support initiation and persistence of cancer. Many of these are involved in the regulation of mitochondrial morphology, mitochondrial apoptosis, mitochondrial calcium homeostasis, mitochondrial associated membranes (MAMs), and retrograde ROS signalling. This review will aim to both explore how kinase signalling integrates with these critical mitochondrial pathways and highlight how these systems can be usurped to support the development of disease. In addition, we will identify areas which require further investigation to fully understand the complexities of these regulatory interactions. Overall, this review will emphasize how studying the interaction between kinase signalling and mitochondria improves our understanding of mitochondrial homeostasis and can yield novel therapeutic targets to treat disease.
    Keywords:  apoptosis; disease adaptation; kinase; mitochondria; mitochondrial associated endoplasmic reticulum membranes (MAMs); mitochondrial morphology; reactive oxygen species (ROS)
    DOI:  https://doi.org/10.3389/fmolb.2024.1354682
  9. Cell Rep. 2024 Mar 06. pii: S2211-1247(24)00191-8. [Epub ahead of print]43(3): 113863
    Integrated stress response signaling acts as a metabolic sensor in fat tissues to regulate oocyte maturation and ovulation.
    Lydia Grmai, Manuel Michaca, Emily Lackner, Narayanan Nampoothiri V P, Deepika Vasudevan.
      Reproduction is an energy-intensive process requiring systemic coordination. However, the inter-organ signaling mechanisms that relay nutrient status to modulate reproductive output are poorly understood. Here, we use Drosophila melanogaster as a model to establish the integrated stress response (ISR) transcription factor, Atf4, as a fat tissue metabolic sensor that instructs oogenesis. We demonstrate that Atf4 regulates lipase activity to mediate yolk lipoprotein synthesis in the fat body. Depletion of Atf4 in the fat body also blunts oogenesis recovery after amino acid deprivation and re-feeding, suggestive of a nutrient-sensing role for Atf4. We also discovered that Atf4 promotes secretion of a fat-body-derived neuropeptide, CNMamide, which modulates neural circuits that promote egg-laying behavior (ovulation). Thus, we posit that ISR signaling in fat tissue acts as a "metabolic sensor" that instructs female reproduction-directly by impacting yolk lipoprotein production and follicle maturation and systemically by regulating ovulation.
    Keywords:  Atf4; CNMa; CP: Cell biology; CP: Developmental biology; adipocyte; bmm; egg retention; integrated stress response; oogenesis; ovulation; yolk protein
    DOI:  https://doi.org/10.1016/j.celrep.2024.113863
  10. Aging (Albany NY). 2024 Mar 04. 16
    PR55α-controlled protein phosphatase 2A inhibits p16 expression and blocks cellular senescence induction by γ-irradiation.
    Chitra Palanivel, Lepakshe S V Madduri, Ashley L Hein, Christopher B Jenkins, Brendan T Graff, Alison L Camero, Sumin Zhou, Charles A Enke, Michel M Ouellette, Ying Yan.
      Cellular senescence is a permanent cell cycle arrest that can be triggered by both internal and external genotoxic stressors, such as telomere dysfunction and DNA damage. The execution of senescence is mainly by two pathways, p16/RB and p53/p21, which lead to CDK4/6 inhibition and RB activation to block cell cycle progression. While the regulation of p53/p21 signaling in response to DNA damage and other insults is well-defined, the regulation of the p16/RB pathway in response to various stressors remains poorly understood. Here, we report a novel function of PR55α, a regulatory subunit of PP2A Ser/Thr phosphatase, as a potent inhibitor of p16 expression and senescence induction by ionizing radiation (IR), such as γ-rays. The results show that ectopic PR55α expression in normal pancreatic cells inhibits p16 transcription, increases RB phosphorylation, and blocks IR-induced senescence. Conversely, PR55α-knockdown by shRNA in pancreatic cancer cells elevates p16 transcription, reduces RB phosphorylation, and triggers senescence induction after IR. Furthermore, this PR55α function in the regulation of p16 and senescence is p53-independent because it was unaffected by the mutational status of p53. Moreover, PR55α only affects p16 expression but not p14 (ARF) expression, which is also transcribed from the same CDKN2A locus but from an alternative promoter. In normal human tissues, levels of p16 and PR55α proteins were inversely correlated and mutually exclusive. Collectively, these results describe a novel function of PR55α/PP2A in blocking p16/RB signaling and IR-induced cellular senescence.
    Keywords:  CDKN2A locus; PP2A; PR55α; RB; p14; p16; p53; γ-irradiation
    DOI:  https://doi.org/10.18632/aging.205619
  11. Gene. 2024 Mar 01. pii: S0378-1119(24)00218-X. [Epub ahead of print]910 148337
    Mitochondrial DNA mutations in extremely preterm infants with bronchopulmonary dysplasia.
    Jiyoon Jeong, Yeonmi Lee, Jongsuk Han, Eunju Kang, Deokhoon Kim, Ki-Soo Kim, Ellen Ai-Rhan Kim, Byong Sop Lee, Euiseok Jung.
      Bronchopulmonary dysplasia (BPD) is a serious chronic lung disease affecting extremely preterm infants. While mitochondrial dysfunction has been investigated in various medical conditions, limited research has explored mitochondrial DNA (mtDNA) gene mutations, specifically in BPD. This study aimed to evaluate mitochondrial mtDNA gene mutations in extremely preterm infants with BPD. In this prospective observational study, we enrolled a cohort of extremely preterm infants diagnosed with BPD. Clinical data were collected to provide comprehensive patient profiles. Peripheral blood mononuclear cells were isolated from whole-blood samples obtained within a defined timeframe. Subsequently, mtDNA extraction and sequencing using next-generation sequencing technology were performed to identify mtDNA gene mutations. Among the cohort of ten extremely preterm infants with BPD, mtDNA sequencing revealed the presence of mutations in seven patients, resulting in a total of twenty-one point mutations. Notably, many of these mutations were identified in loci associated with critical components of the respiratory chain complexes, vital for proper mitochondrial function and cellular energy production. This pilot study provides evidence of mtDNA point mutations in a subset of extremely preterm infants with BPD. These findings suggest a potential association between mitochondrial dysfunction and the pathogenesis of BPD. Further extensive investigations are warranted to unravel the mechanisms underlying mtDNA mutations in BPD.
    Keywords:  Bronchopulmonary dysplasia; Chronic lung disease; Electron transport chain; Gene mutations; Mitochondrial DNA; Preterm infants
    DOI:  https://doi.org/10.1016/j.gene.2024.148337
  12. Nat Commun. 2024 Mar 04. 15(1): 1965
    NDUFS4 regulates cristae remodeling in diabetic kidney disease.
    Koki Mise, Jianyin Long, Daniel L Galvan, Zengchun Ye, Guizhen Fan, Rajesh Sharma, Irina I Serysheva, Travis I Moore, Collene R Jeter, M Anna Zal, Motoo Araki, Jun Wada, Paul T Schumacker, Benny H Chang, Farhad R Danesh.
      The mitochondrial electron transport chain (ETC) is a highly adaptive process to meet metabolic demands of the cell, and its dysregulation has been associated with diverse clinical pathologies. However, the role and nature of impaired ETC in kidney diseases remains poorly understood. Here, we generate diabetic mice with podocyte-specific overexpression of Ndufs4, an accessory subunit of mitochondrial complex I, as a model investigate the role of ETC integrity in diabetic kidney disease (DKD). We find that conditional male mice with genetic overexpression of Ndufs4 exhibit significant improvements in cristae morphology, mitochondrial dynamics, and albuminuria. By coupling proximity labeling with super-resolution imaging, we also identify the role of cristae shaping protein STOML2 in linking NDUFS4 with improved cristae morphology. Together, we provide the evidence on the central role of NDUFS4 as a regulator of cristae remodeling and mitochondrial function in kidney podocytes. We propose that targeting NDUFS4 represents a promising approach to slow the progression of DKD.
    DOI:  https://doi.org/10.1038/s41467-024-46366-w
  13. Nat Chem Biol. 2024 Mar 06.
    Mitochondrial ATP generation is more proteome efficient than glycolysis.
    Yihui Shen, Hoang V Dinh, Edward R Cruz, Zihong Chen, Caroline R Bartman, Tianxia Xiao, Catherine M Call, Rolf-Peter Ryseck, Jimmy Pratas, Daniel Weilandt, Heide Baron, Arjuna Subramanian, Zia Fatma, Zong-Yen Wu, Sudharsan Dwaraknath, John I Hendry, Vinh G Tran, Lifeng Yang, Yasuo Yoshikuni, Huimin Zhao, Costas D Maranas, Martin Wühr, Joshua D Rabinowitz.
      Metabolic efficiency profoundly influences organismal fitness. Nonphotosynthetic organisms, from yeast to mammals, derive usable energy primarily through glycolysis and respiration. Although respiration is more energy efficient, some cells favor glycolysis even when oxygen is available (aerobic glycolysis, Warburg effect). A leading explanation is that glycolysis is more efficient in terms of ATP production per unit mass of protein (that is, faster). Through quantitative flux analysis and proteomics, we find, however, that mitochondrial respiration is actually more proteome efficient than aerobic glycolysis. This is shown across yeast strains, T cells, cancer cells, and tissues and tumors in vivo. Instead of aerobic glycolysis being valuable for fast ATP production, it correlates with high glycolytic protein expression, which promotes hypoxic growth. Aerobic glycolytic yeasts do not excel at aerobic growth but outgrow respiratory cells during oxygen limitation. We accordingly propose that aerobic glycolysis emerges from cells maintaining a proteome conducive to both aerobic and hypoxic growth.
    DOI:  https://doi.org/10.1038/s41589-024-01571-y
  14. Cancer Sci. 2024 Mar 03.
    Mitochondrial fission enhances IL-6-induced metastatic potential in ovarian cancer via ERK1/2 activation.
    Juwon Lee, Youngjin Han, Soochi Kim, HyunA Jo, Wenyu Wang, Untack Cho, Se Ik Kim, Boyun Kim, Yong Sang Song.
      Ovarian cancer is a lethal gynecologic cancer mostly diagnosed in an advanced stage with an accumulation of ascites. Interleukin-6 (IL-6), a pro-inflammatory cytokine is highly elevated in malignant ascites and plays a pleiotropic role in cancer progression. Mitochondria are dynamic organelles that undergo fission and fusion in response to external stimuli and dysregulation in their dynamics has been implicated in cancer progression and metastasis. Here, we investigate the effect of IL-6 on mitochondrial dynamics in ovarian cancer cells (OVCs) and its impact on metastatic potential. Treatment with IL-6 on ovarian cancer cell lines (SKOV3 and PA-1) led to an elevation in the metastatic potential of OVCs. Interestingly, a positive association was observed between dynamin-related protein 1 (Drp1), a regulator of mitochondrial fission, and IL-6R in metastatic ovarian cancer tissues. Additionally, IL-6 treatment on OVCs was linked to the activation of Drp1, with a notable increase in the ratio of the inhibitory form p-Drp1(S637) to the active form p-Drp1(S616), indicating enhanced mitochondrial fission. Moreover, IL-6 treatment triggered the activation of ERK1/2, and inhibiting ERK1/2 mitigated IL-6-induced mitochondrial fission. Suppressing mitochondrial fission through siRNA transfection and a pharmacological inhibitor reduced the IL-6-induced migration and invasion of OVCs. This was further supported by 3D invasion assays using patient-derived spheroids. Altogether, our study suggests the role of mitochondrial fission in the metastatic potential of OVCs induced by IL-6. The inhibition of mitochondrial fission could be a potential therapeutic approach to suppress the metastasis of ovarian cancer.
    Keywords:  Drp13; IL-62; metastasis5; mitochondria1; ovarian cancer4
    DOI:  https://doi.org/10.1111/cas.16064
  15. Sci Total Environ. 2024 Mar 04. pii: S0048-9697(24)01564-X. [Epub ahead of print]923 171423
    Association between ambient particulate matter exposure and mitochondrial DNA copy number: A systematic review and meta-analysis.
    Jian-Chao Qiao, Liang-Jie Sun, Meng-Yue Zhang, Si-Yu Gui, Xin-Chen Wang, Cheng-Yang Hu.
      BACKGROUND: Ambient particulate matter (PM) has been recognized as inducing oxidative stress, which could contribute to mitochondrial damage and dysfunction. However, studies investigating the association between ambient PM and mitochondria, particularly mitochondrial DNA copy number (mtDNA-CN), have yielded inconsistent results.METHODS: We conducted comprehensive literature searches to identify observational studies published before July 17, 2023, examining the association between ambient PM exposure and mtDNA-CN. Meta-analysis using random effects model was employed to calculate the pooled effect estimates for general individual exposures, as well as for prenatal exposure with specific trimester. Additionally, the quality and level of evidence for each exposure-outcome pair was evaluated.
    RESULTS: A total of 10 studies were included in the systematic review and meta-analysis. The results indicated that general individual exposure to PM2.5 (β = -0.084, 95 % CI: -0.521, 0.353; I2 = 93 %) and PM10 (β = 0.035, 95 % CI: -0.129, 0.199; I2 = 95 %) did not significantly affect mtDNA-CN. Prenatal exposure to PM2.5 (β = 0.023, 95 % CI: -0.087, 0.133; I2 = 0 %) and PM10 (β = 0.006, 95 % CI: -0.135; 0.147; I2 = 51 %) were also not significantly associated with mtDNA-CN in offspring. The level of evidence for each tested exposure-outcome pair was assessed as "inadequate."
    CONCLUSIONS: The findings of this systematic review and meta-analysis indicate that there is an "inadequate" strength of evidence for the association between general individual or prenatal exposure to ambient PM and mtDNA-CN. Future research necessitates studies with more rigorous design, enhanced control of confounding factors, and improved measures of exposure to substantiate our findings.
    Keywords:  Ambient air pollution; Meta-analysis; Mitochondrial DNA copy number; Particulate matter; mtDNA
    DOI:  https://doi.org/10.1016/j.scitotenv.2024.171423
  16. Mol Biol Rep. 2024 Mar 05. 51(1): 387
    Crosstalk between vault RNAs and innate immunity.
    Rodolfo Gamaliel Avila-Bonilla, Juan Pablo Martínez-Montero.
      PURPOSE: Vault (vt) RNAs are noncoding (nc) RNAs transcribed by RNA polymerase III (RNA Pol III) with 5'-triphosphate (5'-PPP) termini that play significant roles and are recognized by innate immune sensors, including retinoic acid-inducible protein 1 (RIG-I). In addition, vtRNAs adopt secondary structures that can be targets of interferon-inducible protein kinase R (PKR) and the oligoadenylate synthetase (OAS)/RNase L system, both of which are important for activating antiviral defenses. However, changes in the expression of vtRNAs have been associated with pathological processes that activate proinflammatory pathways, which influence cellular events such as differentiation, aging, autophagy, apoptosis, and drug resistance in cancer cells.RESULTS: In this review, we summarized the biology of vtRNAs and focused on their interactions with the innate immune system. These findings provide insights into the diverse roles of vtRNAs and their correlation with various cellular processes to improve our understanding of their biological functions.
    Keywords:  Innate immunity; RIG-I and PKR; Vault RNAs
    DOI:  https://doi.org/10.1007/s11033-024-09305-y
This page is being maintained by Thomas Krichel. It was last updated on 2024‒03‒19 at 15:06.