Biology subjects

Jekabsone, A.

Publications and source records attributed to Jekabsone, A..

3 recordsLinked to original sources

bioRxiv2024

Psoriasis-like inflammation induces mitochondrial function and structure changes in human keratinocytes and fibroblasts

Mitochondrial structural and functional changes accompany psoriasis, yet the mitochondrial response to psoriatic inflammation in keratinocytes and fibroblasts remains unexplored. In this study, we investigated the effect of psoriasis-like inflammation (PLI) induced by a cytokine cocktail (interleukin (IL)-17A, IL-22 and tumour necrosis factor (TNF)-) on mitochondrial network morphology and function in cultured keratinocytes (HaCaT) and fibroblasts (BJ-5ta). In both cell types, PLI triggered expression of psoriasis-related Elafin and high amounts of cytokines (IL-1, IL-6), interferons (IFN-, IFN-{beta}, IFN-{gamma}) and chemokines (C-C motif chemokine 5 (CCL5) and IL-8), accompanied by increased mitochondrial membrane potential, reactive oxygen species (ROS) production, respiration suppression, network fragmentation, swelling, and cristae disassembly. Stimulated emission depletion (STED) nanoscopy revealed the disappearance of mitochondrial cristae in response to PLI, with the process starting more quickly and being more pronounced in keratinocytes than in fibroblasts. These findings highlight cell-specific mitochondrial responses to psoriatic inflammation, guiding future investigations towards new pharmacological targets for managing psoriasis. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=197 SRC="FIGDIR/small/611357v2_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@153d89org.highwire.dtl.DTLVardef@7b26dcorg.highwire.dtl.DTLVardef@13436c9org.highwire.dtl.DTLVardef@f8f900_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2024

ER-mitochondria distance is a critical parameter for efficient mitochondrial Ca2+ uptake and oxidative metabolism.

IP3 receptor (IP3R)-mediated Ca2+ transfer at the mitochondria-endoplasmic reticulum (ER) contact sites (MERCS) drives mitochondrial Ca2+ uptake and oxidative metabolism and is linked to different pathologies, including Parkinsons disease (PD). The dependence of Ca2+ transfer efficiency on the ER-mitochondria distance remains unexplored. Employing molecular rulers that stabilize ER-mitochondrial distances at 5 nm resolution, and using genetically-encoded Ca2+ indicators targeting the ER lumen and the sub-mitochondrial compartments, we now show that a distance of [~]20 nm is optimal for Ca2+ transfer and mitochondrial oxidative metabolism due to enrichment of IP3R at MERCS. In human iPSC-derived astrocytes from PD patients, 20 nm MERCS were specifically reduced which correlated with a reduction of mitochondrial Ca2+ uptake. Our work determines with precision the optimal distance for Ca2+ flux between ER and mitochondria and suggests a new paradigm for fine control over mitochondrial function.

cell biology↗

bioRxiv2023

Comparison of mitochondrial response to SARS-CoV-2 spike protein receptor binding domain in human lung microvascular, coronary artery endothelial and bronchial epithelial cells

Recent evidence indicate that SARS-CoV-2 spike protein affects mitochondria with a cell type-dependent outcome. We elucidate the effect of SARS-CoV-2 receptor binding domain (RBD) on the mitochondrial network and cristae morphology, oxygen consumption, mitoROS production, and inflammatory cytokine expression in cultured human lung microvascular (HLMVEC) and coronary artery endothelial (HCAEC) and bronchial epithelial cells (HBEC). Live Mito Orange staining, STED microscopy and Fiji MiNa analysis were used for mitochondrial cristae and network morphometry, Agilent XFp analyser for mitochondrial/glycolytic activity, MitoSOX fluorescence for mitochondrial ROS, and qRT-PCR plus Luminex for cytokines. In HLMVEC, SARS-CoV-2 RBD fragmented the mitochondrial network, decreased cristae density, mitochondrial oxygen consumption and glycolysis and induced mitoROS-mediated GM-CSF and IL-1{beta} expression in all three investigated cell types and IL-8 - in both endothelial cell types. Mitochondrial ROS control SARS-CoV-2 RBD-induced inflammation in HLMVEC, HCAEC and HBEC, with the mitochondria of HLMVEC being more sensitive to SARS-CoV-2 RBD.

immunology↗