In order to assess the impact of nitrogen availability on lipid metabolism of Streptomyces coelicolor, we first assessed the global lipid content of 21 strains derived from S. coelicolor M145 deleted for at least one gene involved in nitrogen metabolism. This study revealed that only 7 strains deleted either for genes encoding, proteins involved in polyamine (GlnA2/SCO2241, GlnA3/SCO6962, GlnA4/SCO1613) or protein (Pup/SCO1646) degradation, for the global regulator DasR/SCO5231 that controls negatively the degradation of N acetylglucosamine, a constituant of peptidoglycan, or for two proteins involved in the regulation of nitrogen metabolism, GlnE/SCO2234 and GlnK/SCO5584, had a higher triacylglycerol content than the original strain whereas 5 of these strains (with the exception of glnA2 and pup mutant strains) had a lower cardiolipin content than the original strain. Furthermore, the determination of the level of production of the blue polyketide, actinorhodin (ACT), of these 7 strains grown either in phosphate (Pi) limitation or proficiency, revealed that ACT production was totally abolished in the dasR mutant in both Pi conditions whereas the deletion of pup, glnA2, glnA3 and glnA4 was correlated with a significant increase of total ACT production, in Pi limitation. However, in Pi proficiency, ACT production was only slightly enhanced in the pup, glnA2 and glnA4 mutants and was strongly reduced in the glnA3 mutant. Altogether our data suggest that high TAG and ACT biosynthesis and low cardiolipin biosynthesis might all contribute to the lowering of oxidative stress resulting from nitrogen limitation or from other causes.

Cardiolipin (CL), an essential phospholipid, is localized in the mitochondrial inner membrane, where it plays a critical role in oxidative phosphorylation (OXPHOS) and energy metabolism. This study reviews current findings on cardiolipin's function within neurodegenerative diseases (NDDs), focusing on Alzheimer's and Parkinson's diseases, along with Barth Syndrome. Using lipidomics and protein-lipid interaction analysis, we examine the role of CL in mitochondrial integrity and neuronal function. The primary objective is to analyze how alterations in CL composition and distribution can serve as biomarkers and therapeutic targets for NDDs. Results highlight significant insights into the potential for CL-targeted therapies.

According to many research groups, high glucose induces over production of superoxide anions, and reactive oxygen species (ROS) in general is the link between high glucose levels and the toxicities seen at cellular levels. Respiratory complex anomalies could lead to the production of ROS. Calcium [Ca2+], at physiological levels serves as a second messenger in many physiological functions. Accordingly, mitochondrial calcium [Ca2+]m overload leads to ROS production which could be lethal to the mitochondria through various mechanisms. The F1F0-ATPase (ATP syn-thase or complex V) is the enzyme that is responsible for catalyzing the final step of oxidative phosphorylation. It does so by coupling the translocation of protons in the mitochondrial in-termembrane space and shuttling them to the mitochondrial matrix for ATP synthesis to take place. Mitochondrial complex V T8993G mutation specifically blocks the translocation of protons across the intermembrane space thereby blocking ATP synthesis leading to Neuropathy, Ataxia and Retinitis Pigmentosa Syndromes (NARP). This study seeks to explore the possibility of [Ca2+]m overload mediating the pathological roles of high glucose in defective respiratory chain mediated mitochondrial stress. The NARP cybrids are the in vitro experimental models for the cells with F1FO-ATPase defects, these cells harbor 98% of mtDNA T8993G mutation. Their coun-terparts 143B osteosarcoma cell lines are the parental cell lines used for comparisons. We uncov-ered that, NARP cells mediated and enhanced the death of the cells (apoptosis) when incubated with hydrogen peroxide (H2O2) and high glucose respectively as depicted by the MTT assay of cell viability. Furthermore, using the fluorescence probe-coupled laser scanning confocal imag-ing microscopy, NARP cells significantly enabled mitochondrial reactive oxygen species (mROS) formation and enhanced the depolarization of the mitochondrial membrane potential (ΔΨm). Elucidating the mechanisms of sugar enhanced toxicity on mitochondria would help in the fu-ture to alleviate the symptoms of patients associated with (NARP) syndromes.