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This manuscript uses idealized AGCM experiments to explore impacts of observed decadal Atlantic sea surface temperature (SST) changes on El Nino Southern Oscillation teleconnections. Significant regional changes are observed in numerous locations (e.g., Indo‐Pacific and Central Africa) due to the addition of the AMV anomalies. In some regions the teleconnection impacts of AMV forcing appeared to scale with the magnitude of the AMV forcing. However, the AMV induced modulation of temperature and precipitation teleconnections is regionally specific with changes in magnitude, statistical strength, and spatial connection dependent on region. These ENSO teleconnection changes were found to be asymmetric between AMV phases, with negative anomalies appearing to have a larger effect. We hypothesize these changes may be underpinned by a AMV induced modulation and migration of ENSO's equatorial precipitation response. Plain Language Summary: The potential of the Atlantic sea surface temperature (SST) mean state to impact the El Nino Southern Oscillation (ENSO) is analyzed over 24 years using global climate models with different forced Atlantic Ocean mean states. Typical teleconnections of ENSO are investigated finding a significant change in numerous areas which are not found to be globally consistent. Greatest impacts are found to be regionally specific with negative Atlantic anomalies suggested to have a greater impact. In some locations influence was found to scale with the magnitude of the introduced anomaly. It is theorised that these changes are underpinned by a spatial migration in the typical ENSO equatorial precipitation response between different mean states of the Atlantic Ocean. Key Points: Atlantic Multidecadal Variability SSTA can produce statistically significant changes of ENSO teleconnections without any changes in ENSOENSO teleconnection modulation by the AMV was regionally specific with variation in statistical strength and sign relative to the controlTeleconnection modulation is likely a result of tropical Pacific precipitation changes during ENSO induced atmospheric stability changes [ABSTRACT FROM AUTHOR]

The MICOS complex, essential for cristae organization, comprises MIC10 and MIC60 subcomplexes, with MIC13 as a crucial subunit. MIC13 mutations cause severe mitochondrial hepato-encephalopathy, cristae defects, and MIC10-subcomplex loss. We demonstrate that depletion of the mitochondrial protease YME1L in MIC13 KO stabilizes MIC10-subcomplex, restoring MIC60-MIC10 interaction and crista junction (CJ) defects, indicating MIC13 is crucial for MIC10-subcomplex stabilization rather than MIC60-MIC10 bridging. We identified stomatin-like protein 2 (SLP2) as a key MIC13 interaction partner, essential for cristae morphology and CJ formation. SLP2 serves as an interaction hub for MICOS subunits and stabilizes MIC26 by protecting it from YME1L-mediated degradation. Deleting both SLP2 and MIC13 impairs MIC60-subcomplex assembly and its nanoscale organization. Restoring the MIC10-subcomplex in MIC13-SLP2 double KO cells through YME1L depletion reinstates MIC60-subcomplex assembly and cristae morphology. Overall, we propose SLP2 and the MIC10-subcomplex act as a proteolytically controlled 'seeder' complex, facilitating MICOS-MIB complex assembly and maintaining mitochondrial integrity., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Mitochondria play central roles in metabolism and metabolic disorders such as type 2 diabetes. MIC26, a mitochondrial contact site and cristae organising system complex subunit, was linked to diabetes and modulation of lipid metabolism. Yet, the functional role of MIC26 in regulating metabolism under hyperglycemia is not understood. We used a multi-omics approach combined with functional assays using WT and MIC26 KO cells cultured in normoglycemia or hyperglycemia, mimicking altered nutrient availability. We show that MIC26 has an inhibitory role in glycolysis and cholesterol/lipid metabolism under normoglycemic conditions. Under hyperglycemia, this inhibitory role is reversed demonstrating that MIC26 is critical for metabolic adaptations. This is partially mediated by alterations of mitochondrial metabolite transporters. Furthermore, MIC26 deletion led to a major metabolic rewiring of glutamine use and oxidative phosphorylation. We propose that MIC26 acts as a metabolic "rheostat," that modulates mitochondrial metabolite exchange via regulating mitochondrial cristae, allowing cells to cope with nutrient overload., (© 2024 Damiecki et al.)

Impairments of mitochondrial functions are linked to human ageing and pathologies such as cancer, cardiomyopathy, neurodegeneration and diabetes. Specifically, aberrations in ultrastructure of mitochondrial inner membrane (IM) and factors regulating them are linked to diabetes. The development of diabetes is connected to the 'Mitochondrial Contact Site and Cristae Organising System' (MICOS) complex which is a large membrane protein complex defining the IM architecture. MIC26 and MIC27 are homologous apolipoproteins of the MICOS complex. MIC26 has been reported as a 22 kDa mitochondrial and a 55 kDa glycosylated and secreted protein. The molecular and functional relationship between these MIC26 isoforms has not been investigated. In order to understand their molecular roles, we depleted MIC26 using siRNA and further generated MIC26 and MIC27 knockouts (KOs) in four different human cell lines. In these KOs, we used four anti-MIC26 antibodies and consistently detected the loss of mitochondrial MIC26 (22 kDa) and MIC27 (30 kDa) but not the loss of intracellular or secreted 55 kDa protein. Thus, the protein assigned earlier as 55 kDa MIC26 is nonspecific. We further excluded the presence of a glycosylated, high-molecular weight MIC27 protein. Next, we probed GFP- and myc-tagged variants of MIC26 with antibodies against GFP and myc respectively. Again, only the mitochondrial versions of these tagged proteins were detected but not the corresponding high-molecular weight MIC26, suggesting that MIC26 is indeed not post-translationally modified. Mutagenesis of predicted glycosylation sites in MIC26 also did not affect the detection of the 55 kDa protein band. Mass spectrometry of a band excised from an SDS gel around 55 kDa could not confirm the presence of any peptides derived from MIC26. Taken together, we conclude that both MIC26 and MIC27 are exclusively localized in mitochondria and that the observed phenotypes reported previously are exclusively due to their mitochondrial function., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lubeck et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Emergency Management System (EMS) is an important component of Intelligent transportation systems, and its primary objective is to send Emergency Vehicles (EVs) to the location of a reported incident. However, the increasing traffic in urban areas, especially during peak hours, results in the delayed arrival of EVs in many cases, which ultimately leads to higher fatality rates, increased property damage, and higher road congestion. Existing literature addressed this issue by giving higher priority to EVs while traveling to an incident place by changing traffic signals (e.g., making the signals green) on their travel path. A few works have also attempted to find the best route for an EV using traffic information (e.g., number of vehicles, flow rate, and clearance time) at the beginning of the journey. However, these works did not consider congestion or disruption faced by other non-emergency vehicles adjacent to the EV travel path. The selected travel paths are also static and do not consider changing traffic parameters while EVs are en route. To address these issues, this article proposes an Unmanned Aerial Vehicle (UAV) guided priority-based incident management system to assist EVs in obtaining a better clearance time in intersections and thus achieve a lower response time. The proposed model also considers disruption faced by other surrounding non-emergency vehicles adjacent to the EVs' travel path and selects an optimal solution by controlling the traffic signal phase time to ensure that EVs can reach the incident place on time while causing minimal disruption to other on-road vehicles. Simulation results indicate that the proposed model achieves an 8% lower response time for EVs while the clearance time surrounding the incident place is improved by 12%.

Mitochondrial ultrastructure is highly adaptable and undergoes dynamic changes upon physiological and energetic cues. MICOS (mitochondrial contact site and cristae organizing system), a large oligomeric protein complex, maintains mitochondrial ultrastructure as it is required for formation of crista junctions (CJs) and contact sites. MIC13 acts as a critical bridge between two MICOS subcomplexes. Deletion of MIC13 causes loss of CJs resulting in cristae accumulating as concentric rings and specific destabilization of the MIC10-subcomplex. Mutations in MIC13 are associated with infantile lethal mitochondrial hepato-encephalopathy, yet functional regions within MIC13 were not known. To identify and characterize such regions, we systemically generated 20 amino-acids deletion variants across the length of MIC13. While deletion of many of these regions of MIC13 is dispensable for its stability, the N-terminal region and a stretch between amino acid residues 84 and 103 are necessary for the stability and functionality of MIC13. We could further locate conserved motifs within these regions and found that a GxxxG motif in the N-terminal transmembrane segment and an internal WN motif are essential for stability of MIC13, formation of the MIC10-subcomplex, interaction with MIC10- and MIC60-subcomplexes and maintenance of cristae morphology. The GxxxG motif is required for membrane insertion of MIC13. Overall, we systematically found important conserved residues of MIC13 that are required to perform the bridging between the two MICOS subcomplexes. The study improves our understanding of the basic molecular function of MIC13 and has implications for its role in the pathogenesis of a severe mitochondrial disease., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: Oxidative stress has been hypothesized as a central component of both placental and endothelial dysfunction, leading to PE. This oxidative stress leading to mitochondrial dysfunction may be due to variations in mtDNA copy numbers as an adaptive response. In the present study we aimed to analyse mtDNA copy numbers in the placenta obtained after delivery from the women with PE as compared to the controls., Study Design: It was a prospective case control study. A total of 32 placental samples were analyzed (Cases: 17; Controls: 15). Samples were collected ex vivo, after childbirth. MtDNA content was determined useing real-time quantitative PCR qRT-PCR) using TaqMan probes designed for two genes: MT-ND1 and a mitochondrial gene encoding for the NADH dehydrogenase 1 protein., Results: We found that the median (IQR) mtDNA copy number was higher in PE cases 24.32 (9.260-33.51) as compared with controls 20.32 (13.33-26.22). On subgroup analysis, the median (IQR) mtDNA copy number was higher in early onset PE 28.06 (20.80-36.87) as compared to late onset PE 9.215 (4.150-56.45) as well as the controls 20.32 (13.33-26.22)., Conclusion: Our findings support a higher mtDNA copy number in early onset PE as compared to late onset PE and control population. Although, mtDNA may only be increased in very severe cases of early onset preeclampsia. Future research may be directed to ascertain if mtDNA copy numbers can be a novel biomarker to predict or prognosticate early onset preeclampsia., (Copyright © 2020 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide is a major public health concern. Cancer patients are considered a vulnerable population to SARS-CoV-2 infection and may develop several COVID-19 symptoms. The heightened immunocompromised state, prolonged chronic pro-inflammatory milieu coupled with comorbid conditions are shared in both disease conditions and may influence patient outcome. Although ovarian cancer (OC) and COVID-19 are diseases of entirely different primary organs, both diseases share similar molecular and cellular characteristics in their microenvironment suggesting a potential cooperativity leading to poor outcome. In COVID-19 related cases, hospitalizations and deaths worldwide are lower in women than in males; however, comorbidities associated with OC may increase the COVID-19 risk in women. The women at the age of 50-60 years are at greater risk of developing OC as well as SARS-CoV-2 infection. Increased levels of gonadotropin and androgen, dysregulated renin-angiotensin-aldosterone system (RAAS), hyper-coagulation and chronic inflammation are common conditions observed among OC and severe cases of COVID-19. The upregulation of common inflammatory cytokines and chemokines such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-2, IL-6, IL-10, interferon-γ-inducible protein 10 (IP-10), granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein-1 (MCP-1), macrophage colony-stimulating factor (M-CSF), among others in the sera of COVID-19 and OC subjects suggests potentially similar mechanism(s) involved in the hyper-inflammatory condition observed in both disease states. Thus, it is conceivable that the pathogenesis of OC may significantly contribute to the potential infection by SARS-CoV-2. Our understanding of the influence and mechanisms of SARS-CoV-2 infection on OC is at an early stage and in this article, we review the underlying pathogenesis presented by various comorbidities of OC and correlate their influence on SARS-CoV-2 infection.

Intrauterine Growth Restriction (IUGR) is a common and significant complication that arises during pregnancy wherein the fetus fails to attain its full growth potential. Mitochondria being one of the primary sources of energy, plays an important role in placentation and fetal development. In IUGR pregnancy, increased oxidative stress due to inadequate oxygen and nutrient supply could possibly alter mitochondrial functions and homeostasis. In this study, we evaluated the biochemical and molecular changes in mitochondria as biosignature for early and better characterization of IUGR pregnancies. We identified significant increase in mtDNA copy number in both IUGR (p = 0.0001) and Small for Gestational Age (SGA) but healthy (p = 0.0005) placental samples when compared to control. Whole mitochondrial genome sequencing identified novel mutations in both coding and non-coding regions of mtDNA in multiple IUGR placental samples. Sirtuin-3 (Sirt3) protein expression was significantly downregulated (p = 0.027) in IUGR placenta but there was no significant difference in Nrf1 expression in IUGR when compared to control group. Our study provides an evidence for altered mitochondrial homeostasis and paves a way towards interrogating mitochondrial abnormalities in IUGR pregnancies., (Copyright © 2020 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

Background: Neurodegenerative disorders such as hereditary ataxia often manifest overlapping symptoms and are likely to be misdiagnosed based on clinical phenotypes. To identify the genes associated with such disorders for diagnostic purposes, geneticists often use high throughput technologies which generate an enormous amount of data on variants whose relevance can be unclear. Besides, analysis and interpretation of high throughput data require gleaning of several web-based resources which can be laborious and time-consuming. To overcome these, we have created a Database for Inherited Ataxia (DINAX), a repository of gene variants from publicly available information., Methods: DINAX is implemented as a MySQL relational database using the PHP scripting language. Web interfaces were developed using HTML, CSS, and JavaScript. Variant and phenotype information was collected and manually curated from published literature and primary databases such as OMIM and ClinVar. These were further analyzed to decipher expression and pathway analysis., Results: DINAX is an inventory of 7166 genomic variants (single nucleotide polymorphisms, deletions, insertions, and translocations) reported till date among the 185 genes associated with different subtypes of inherited ataxia. DINAX implements a dual search methodology for genes and phenotypes linking to ataxia associated genes, variants, and their source. Pathway analysis confirmed their association with ataxia., Conclusion: The database is created to provide a single web source for obtaining information about ataxia related genes. Besides, the database facilitates easy identification of known and reported variants as well as the novel or unreported variants. DINAX is freely available at http://slsdb.manipal.edu/dinax., (Copyright © 2020 Elsevier Ltd. All rights reserved.)