The effect of hyperglycemia on the morphology of individual mitochondria and the state of the mitochondrial network in primary mouse lung microvascular endotheliocytes and human dermal fibroblasts has been investigated. The cells were exposed to high (30 mM) and low (5.5 mM) glucose concentrations for 36 h. In primary endotheliocytes, hyperglycemic stress induced a significant increase in the number of mitochondria and a decrease in the interconnectivity value of the mitochondrial network, which was associated with a decrease in the mean size of the mitochondria. Analysis of the mRNA level of the genes of proteins responsible for mitochondrial biogenesis and mitophagy revealed an increase in the expression level of the , , and genes, indicating stimulated mitochondrial turnover in endotheliocytes under high glucose conditions. In primary fibroblasts, hyperglycemia caused a decrease in the number of mitochondria and an increase in their size. As a result, the mitochondria exhibited higher values for elongation. In parallel, the mRNA level of the and genes in fibroblasts exposed to hyperglycemia was reduced. These findings indicate that high glucose concentrations induced cell-specific morphological rearrangements of individual mitochondria and the mitochondrial network, which may be relevant during mitochondria-targeted drug testing and therapy for hyperglycemic and diabetic conditions.
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http://dx.doi.org/10.3390/ijms241512485 | DOI Listing |
J Inflamm Res
December 2024
Department of Cardiothoracic Surgery, Changzheng Hospital, Naval Medical University, Shanghai, People's Republic of China.
Background: Cardiac macrophages are a heterogeneous population with high plasticity and adaptability, and their mechanisms in heart failure (HF) remain poorly elucidated.
Methods: We used single-cell and bulk RNA sequencing data to reveal the heterogeneity of non-cardiomyocytes and assess the immunoreactivity of each subpopulation. Additionally, we employed four integrated machine learning algorithms to identify macrophage-related genes with diagnostic value, and in vivo validation was performed.
Adv Sci (Weinh)
December 2024
Department of Systems Biology, Beckman Research Institute, City of Hope, 1500 E Duarte Rd, Duarte, CA, 91010, USA.
Cell signaling pathways are enriched for biological processes crucial for cellular communication, response to external stimuli, and metabolism. Here, a cell signaling-focused CRISPR screen identified cytochrome c oxidase subunit 4 isoform 1 (COX4I1) as a novel vulnerability in acute myeloid leukemia (AML). Depletion of COX4I1 hindered leukemia cell proliferation and impacted in vivo AML progression.
View Article and Find Full Text PDFExp Eye Res
December 2024
Departments of Biochemistry and Ophthalmology, University of Washington, Seattle, WA, USA. Electronic address:
Organelles such as mitochondria, lysosomes, peroxisomes, and the endoplasmic reticulum form highly dynamic cellular networks and exchange information through sites of physical contact. While each organelle performs unique functions, this inter-organelle crosstalk helps maintain cell homeostasis. Age-related macular degeneration (AMD) is a devastating blinding disease strongly associated with mitochondrial dysfunction, oxidative stress, and decreased clearance of cellular debris in the retinal pigment epithelium (RPE).
View Article and Find Full Text PDFNat Commun
December 2024
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 65, Stockholm, Sweden.
Aberration of mitochondrial function is a shared feature of many human pathologies, characterised by changes in metabolic flux, cellular energetics, morphology, composition, and dynamics of the mitochondrial network. While some of these changes serve as compensatory mechanisms to maintain cellular homeostasis, their chronic activation can permanently affect cellular metabolism and signalling, ultimately impairing cell function. Here, we use a Drosophila melanogaster model expressing a proofreading-deficient mtDNA polymerase (POLγ) in a genetic screen to find genes that mitigate the harmful accumulation of mtDNA mutations.
View Article and Find Full Text PDFPhytother Res
December 2024
Department of Pharmacy, Shenzhen Children's Hospital, Shenzhen, China.
Glioma is recognized as one of the most lethal and aggressive brain tumors. Although the standard-of-care treatment for glioblastoma (GBM) involves maximal surgical resection and temozolomide (TMZ) chemotherapy, the discovery of novel anti-tumor agents from nature sources is an effective strategy for glioma treatment. In this study, we conducted a screening process to identify the bisindole alkaloid melodinine J (MDJ) from Melodinus tenuicaudatus.
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