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Coenzyme Q (CoQ) is a redox-active lipid molecule that acts as an electron carrier in the mitochondrial electron transport chain. In Saccharomyces cerevisiae, CoQ is synthesized in the mitochondrial matrix by a multisubunit protein-lipid complex termed the CoQ synthome, the spatial positioning of which is coordinated by the endoplasmic reticulum-mitochondria encounter structure (ERMES). The MDM12 gene encoding the cytosolic subunit of ERMES is coexpressed with COQ10, which encodes the putative CoQ chaperone Coq10, via a shared bidirectional promoter. Deletion of COQ10 results in respiratory deficiency, impaired CoQ biosynthesis, and reduced spatial coordination between ERMES and the CoQ synthome. While Coq10 protein content is maintained upon deletion of MDM12, we show that deletion of COQ10 by replacement with a HIS3 marker results in diminished Mdm12 protein content. Since deletion of individual ERMES subunits prevents ERMES formation, we asked whether some or all of the phenotypes associated with COQ10 deletion result from ERMES dysfunction. To identify the phenotypes resulting solely due to the loss of Coq10, we constructed strains expressing a functionally impaired (coq10-L96S) or truncated (coq10-R147∗) Coq10 isoform using CRISPR-Cas9. We show that both coq10 mutants preserve Mdm12 protein content and exhibit impaired respiratory capacity like the coq10Δ mutant, indicating that Coq10s function is vital for respiration regardless of ERMES integrity. Moreover, the maintenance of CoQ synthome stability and efficient CoQ biosynthesis observed for the coq10-R147∗ mutant suggests these deleterious phenotypes in the coq10Δ mutant result from ERMES disruption. Overall, this study clarifies the role of Coq10 in modulating CoQ biosynthesis.

Context: Oocyte vesicles, or vacuoles, have been described using transmission electron microscopy in most species. In sheep and cow oocytes, vesicles constitute up to 30% of the cytoplasm, their volume decreases during maturation and is lower in poorer quality oocytes, suggesting they are important for oocyte competence. However, the composition and function of these organelles is unknown. Aim: This study aimed to ascertain the content of oocyte vesicles and examine the effect of different fixation methods on the size and preservation of these organelles. Methods: Sheep oocytes were centrifuged to segregate organelles then stained with organelle-specific fluorescent dyes (Nile Red, LysoTracker, Fluo-4-AM and TMRM) and imaged by live cell confocal microscopy. The oocytes were fixed with either glutaraldehyde or paraformaldehyde and prepared for electron microscopy to confirm the distribution of organelles and compare ultrastructure and organelle size. Key results: Nile Red staining has identified that vesicles contain lipid that is different to that in the osmium-stained lipid droplets observed by electron microscopy. Lipid droplets and vesicles were significantly smaller when prepared for electron microscopy compared to live cell imaging. Organelles were less likely to be fully segregated following centrifugation in oocytes prior to maturation (20%) compared to oocytes after maturation (77%; P < 0.0001). Conclusions: Oocyte vesicles are lipid storing organelles that may be important for oocyte quality. Implications: This study highlights the importance of lipid for oocyte quality and the need for further research to identify the optimal fatty acid content for in vitro maturation media and oocyte competence. Poor egg (oocyte) quality is a leading cause of reduced fertility in humans and animals. Large vesicles within oocytes appear to be important for oocyte quality in animals but their composition is unknown. Our study has identified that these vesicles, which appear empty in electron micrographs, contain lipid that differs to that contained in classical lipid droplets. This knowledge may be used to improve in vitro maturation media to enhance oocyte quality. Image by K L Reader. This article belongs to the collection: The biology of the ovary – Honouring the contributions of Ken P McNatty and Rex J Scaramuzzi. [ABSTRACT FROM AUTHOR]

Introduction: Diabetes is a metabolic disorder of glucose homeostasis that is a significant risk factor for neurodegenerative diseases, such as Alzheimer's disease, as well as mood disorders, which often precede neurodegenerative conditions. We examined the medial habenulainterpeduncular nucleus (MHb-IPN), as this circuit plays crucial roles in mood regulation, has been linked to the development of diabetes after smoking, and is rich in cholinergic neurons, which are affected in other brain areas in Alzheimer's disease. Methods: This study aimed to investigate the impact of streptozotocin (STZ)-induced hyperglycemia, a type 1 diabetes model, on mitochondrial and lipid homeostasis in 4% paraformaldehyde-fixed sections from the MHb and IPN of C57BL/6 J male mice, using a recently developed automated pipeline for mitochondrial analysis in confocal images. We examined different time points after STZ-induced diabetes onset to determine how the brain responded to chronic hyperglycemia, with the limitation that mitochondria and lipids were not examined with respect to cell type or intracellular location. Results: Mitochondrial distribution and morphology differentially responded to hyperglycemia depending on time and brain area. Six weeks after STZ treatment, mitochondria in the ventral MHb and dorsal IPN increased in number and exhibited altered morphology, but no changes were observed in the lateral habenula (LHb) or ventral IPN. Strikingly, mitochondrial numbers returned to normal dynamics at 12 weeks. Both blood glucose level and glycated hemoglobin (HbA1C) correlated with mitochondrial dynamics in ventral MHb, whereas only HbA1C correlated in the IPN. We also examined lipid homeostasis using BODIPY staining for neutral lipids in this model given that diabetes is associated with disrupted lipid homeostasis. BODIPY staining intensity was unchanged in the vMHb of STZ-treated mice but increased in the IPN and VTA and decreased in the LHb at 12 weeks. Interestingly, areas that demonstrated changes in mitochondria had little change in lipid staining and vice versa. Discussion: This study is the first to describe the specific impacts of diabetes on mitochondria in the MHb-IPN circuit and suggests that the cholinergic MHb is uniquely sensitive to diabetesinduced hyperglycemia. Further studies are needed to understand the functional and behavioral implications of these findings. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is an aging-associated neurodegenerative disorder, characterized by the progressive loss of dopaminergic neurons in the pars compacta of the substantia nigra and the presence of Lewy bodies containing α-synuclein within these neurons. Oligomeric α-synuclein exerts neurotoxic effects through mitochondrial dysfunction, glial cell inflammatory response, lysosomal dysfunction and so on. α-synuclein aggregation, often accompanied by oxidative stress, is generally considered to be a key factor in PD pathology. At present, emerging evidences suggest that metabolism alteration is closely associated with α-synuclein aggregation and PD progression, and improvement of key molecules in metabolism might be potentially beneficial in PD treatment. In this review, we highlight the tripartite relationship among metabolic changes, α-synuclein aggregation, and oxidative stress in PD, and offer updated insights into the treatments of PD, aiming to deepen our understanding of PD pathogenesis and explore new therapeutic strategies for the disease. [ABSTRACT FROM AUTHOR]

Highlights: Coelastrella sp. demonstrated strong lipid production potential, especially at pH 7.0 and 0.5% fertilizer concentration. Stress conditions enhanced lipid accumulation, indicating resilience and adaptability for cultivation. The fatty acid profile supports the use of Coelastrella sp. for sustainable biodiesel production.The study examined the lipid production potential of the freshwater microalga Coelastrella sp., isolated from a pond in Gundur, Tiruchirappalli, Tamil Nadu, India. The alga was cultured in BG-11 medium under different conditions of pH, salinity, and nutrient availability to optimize lipid yield. The cultures were incubated at 25 °C with constant illumination (3000 lx) and aeration for a period of three weeks. The effects of pH levels (6.0, 7.0, 8.0, 9.0), sodium chloride concentrations (0.2 mM to 0.8 mM), sodium nitrate levels (2 mM to 8 mM), and inorganic fertilizer concentrations (0.05% to 2.0%) on biomass and lipid productivity were assessed. The highest biomass productivity (0.199 g/L/day) and lipid productivity (0.108 g/L/day) were observed at pH 7.0, with nitrate concentrations of 0.4 mM yielding the most significant total lipid content (0.102 g/L/day). Optimal salinity was found at 0.8 mM, and fertilizer concentration of 0.5% significantly enhanced biomass and lipid yields, achieving a biomass productivity of 0.200 g/L/day and lipid productivity of 0.115 mg/L. Key findings included increased lipid accumulation under stress conditions, as indicated by Nile Red staining. FTIR analysis revealed the presence of functional groups linked to triacylglycerides (TAGs) and other lipids. Gas chromatography identified noteworthy fatty acids, such as linolelaidic acid (24%), cis-11,14-eicosadienoic acid (17%), and arachidonic acid (11%). Despite the presence of polyunsaturated fatty acids (PUFAs), particularly C18:2, C18:3, and C20:4, which are valuable for nutraceutical and pharmaceutical applications, the study identified fatty acid profile with monounsaturated (MUFA) and saturated fatty acids (SFA) that make Coelastrella sp. a promising candidate for biodiesel production. [ABSTRACT FROM AUTHOR]

Prolonged hyperglycemia conditions are a risk factor for chronic degenerative diseases such as diabetes and obesity. Testosterone is known to cause muscle hypertrophy, reduced fat mass, and increased body strength. The study aimed to verify possible alterations and differences in the influence of testosterone on the physical performance in post-exercise conditions of young and old animals with alloxan-induced hyperglycemia. We randomly assigned 32 young Wistar rats to groups of untreated non-diabetic young, treated non-diabetic young, untreated diabetic young, and treated diabetic young rats, and 32 aged Wistar rats to groups of untreated non-diabetic elderly, treated non-diabetic elderly, untreated diabetic elderly, and treated diabetic elderly rats, with eight animals each group. The treated non-diabetic and treated diabetic groups received injections of 15 mg/kg weight Durateston™. All the trained groups performed aquatic training with an overload of 5% of the body mass. Following the experiment, we anesthetized and euthanized the animals after exercise (exhaustion). Hemoglobin, erythrocytes, and hematocrit values were higher in the treated groups. The treated diabetic elderly group had the highest leukocyte and neutrophil counts compared to the untreated young groups (p < 0.05). As for the lipid profile, untreated rats had the highest values. Glucose concentration was higher at rest and after exercise in the untreated diabetic groups (p < 0.05). Lactate was more elevated in the untreated diabetic groups, and the testosterone-treated groups performed the longest swimming time after the maximal test (p < 0.05). The use of testosterone in conjunction with physical exercise improved physical performance in water, blood glucose, and lipid profiles. [ABSTRACT FROM AUTHOR]

Dysregulated lipid metabolism, characterized by the accumulation of lipid deposits on Bruch's membrane and in drusen, is considered a key pathogenic event in age‐related macular degeneration (AMD). The imbalance of lipid production, usage, and transport in local tissues, particularly in the retinal pigment epithelium (RPE), is increasingly recognized as crucial in AMD development. However, the molecular mechanisms governing lipid metabolism in the RPE remain elusive. LIPIN1, a multifunctional protein acting as both a modulator of transcription factors and a phosphatidate phosphatase (PAP1), is known to play important regulatory roles in lipid metabolism and related biological functions, such as inflammatory responses. While deficits in LIPIN1 have been linked to multiple diseases, its specific roles in the retina and RPE remain unclear. In this study, we investigated LIPIN1 in RPE integrity and function using a tissue‐specific knockout animal model. The clinical and histological examinations revealed age‐dependent degeneration in the RPE and the retina, along with impaired lipid metabolism. Bulk RNA sequencing indicated a disturbance in lipid metabolic pathways. Moreover, these animals exhibited inflammatory markers reminiscent of human AMD features, including deposition of IgG and C3d on Bruch's membrane. Collectively, our findings indicate that LIPIN1 is a critical component of the complex regulatory network of lipid homeostasis in the RPE. Disruption of LIPIN1‐mediated regulation impaired lipid balance and contributed to AMD‐related pathogenic changes. [ABSTRACT FROM AUTHOR]

Background: Excessive submental fat under the chin is a known aesthetic concern because of its negative impact on facial appearance and psychological well-being. AYP-101 is a newly developed injectable agent containing 93% soybean phosphatidylcholine (SPC) designed to reduce submental fat. We conducted a phase 1 study to evaluate the safety, pharmacokinetic (PK), and lipid profile effects of AYP-101. Methods: This study was a randomized, double-blind, placebo-controlled, single-dose, two-cohort trial. Participants were randomized into groups receiving 250 mg of AYP-101, 500 mg of AYP-101, or placebo at a 9:9:8 ratio across both cohorts. Safety was assessed through standard clinical evaluations. Blood samples were collected up to 144 h postdose in cohort 1 and up to 48 h postdose in cohort 2. The PK parameters were calculated via noncompartmental analysis. Results: All 26 randomized subjects completed the study. A total of 72 solicited adverse drug reactions (ADRs) were reported by 24 subjects, all of which were mild. The most common ADRs were injection site pain and bruising. There were 29 ADR cases in the 250 mg group; 26 cases in the 500 mg group; and 18 cases in the placebo group, indicating that there were no clinically significant differences in the safety profiles between the groups. All the dose groups presented similar PK profiles, with Cmax values of 12.86, 13.44, and 13.61 µg/L and AUC0−24 h values of 278.06, 274.79, and 267.63 µg*h/L, respectively. No clinically significant differences in PK or lipid profiles were observed between the postdose group and the baseline group for any of the dose groups. Conclusions: AYP-101 appears to be a safe candidate for treating submental fat, with localized reactions and no systemic exposure at single subcutaneous doses of up to 500 mg. Trial registration: ClinicalTrials.gov NCT05476094. [ABSTRACT FROM AUTHOR]