Biology subjects

Sosnovtseva, O.

Publications and source records attributed to Sosnovtseva, O..

5 recordsLinked to original sources

bioRxiv2026

Mitochondrial cytochrome c accumulation accompanies reduced electron flux through complex IV without enhancing cell sensitivity to apoptosis

We show that chronic impairment of mitochondrial respiration is associated with marked accumulation of cytochrome c (Cytc) protein. Using SCO2-deficient HCT116 cells lacking functional cytochrome c oxidase and wild-type cells exposed to sustained hypoxia, we found that substantial mitochondrial Cytc accumulation parallels reduced electron flux through Cytc. SCO2-deficient cells exhibited equally elevated Cytc levels under normoxia (19% O2) and hypoxia (0.1-3% O2). Wild-type cells under sustained hypoxia accumulated Cytc, reaching levels comparable to those in SCO2-deficient cells. This effect was reversible upon reoxygenation. Increased Cytc protein levels were also observed in other cell models, including primary cortical neurons cultured under chronic hypoxia and in cerebral cortex tissue from hypoxia-exposed mice. Cytc accumulation occurred independently of CYCS transcription, mRNA translation, HIF activation, ROS production and changes in mitochondrial network. Pharmacological inhibition of complex III was likewise accompanied by increased Cytc levels, whereas mitochondrial uncoupling had no effect, suggesting that impaired electron transfer rather than membrane depolarisation per se underlies this association. Raman spectroscopy revealed enrichment of reduced Cytc and an increased Cytc-to-cytochrome b ratio in respiration-deficient cells. Further supporting a stabilisation-based mechanism, the fraction of membrane-unbound ferro-Cytc was decreased in SCO2-deficient cells, consistent with moderate cardiolipin enrichment, which is known to enhance retention of Cytc at the inner mitochondrial membrane. Despite elevated mitochondrial Cytc content, SCO2-deficient cells were less susceptible to apoptosis induced by intermittent hypoxia or dichloroacetate. Together, these findings indicate that reduced electron flux through complex IV is associated with Cytc accumulation through increased protein stability and membrane retention without enhancing apoptotic sensitivity.

Cell Biology↗

bioRxiv2024

Laser speckle imaging of hepatic microcirculation

The liver controls blood homeostasis and depends critically on adequate blood supply. While the global regulation of liver blood flow via the hepatic arterial buffer response is well established, the mechanisms governing hepatic sinusoidal hemodynamics remain elusive. We use laser speckle contrast imaging to investigate the hepatic microvascular blood flow in anesthetized rats. Laser speckle contrast imaging offers a spatial resolution of a few micrometers, enabling visualization of individual microvessels, and a temporal resolution sufficient to track flow dynamics. This allowed us to resolve individual sinusoids and venules on the liver surface and to detect a reduction of the blood flow following local Angiotensin-II injections. We show that the blood flow oscillates with frequencies within the range of 0.05-0.4 Hz, which may be linked to rhythmic contraction of upstream blood vessels. Our findings provide insights into vessel-specific liver microcirculation in vivo, offering new opportunities to explore vascular dysfunction mechanisms in metabolic liver diseases.

physiology↗

bioRxiv2022

The assessment of cortical hemodynamical responses induced by tubuloglomerular feedback using in vivo imaging

The tubuloglomerular feedback (TGF) mechanism is crucial in modulating renal hemodynamics and glomerular filtration rate in individual nephrons. Our study aimed to evaluate the TGF-induced vascular responses by comparing the effects of two transport inhibitors with different sites and mechanisms of action. We assessed cortical hemodynamics with high-resolution laser speckle contrast imaging, which enabled the evaluation of blood flow individual micro-vessels and analysis of their dynamical patterns in the time-frequency domain. We demonstrated that a systemic administration of a loop diuretic abolishes TGF-mediated hemodynamic responses. Furthermore, we showed that the local microcirculatory blood flow decreased, and the TGF reset in response to reduced proximal reabsorption elicited by systemic administration of a sodium-glucose co-transporter 2 inhibitor, phlorizin.

physiology↗

bioRxiv2021

Blood flow synchronization in renal microcirculation - a high-resolution imaging study.

AimsInternephron signalling and interaction are fundamental for kidney function. Earlier studies have shown that nephrons signal to each other over short distances and adjust their activity accordingly. Micropuncture experiments revealed synchronous clusters of 2-3 nephrons formed from such interactions, while imaging and modelling results suggested the possibility of larger clusters. Such clusters are expected to play an important role in renal autoregulation, but their presence has not been confirmed and their size has not been estimated. In this study, we present methodology for high resolution renal blood flow imaging and apply it to estimate frequency and phase angle differences in kidney blood vessels under normal conditions and after administration of the vasoactive agents angiotensin II and acetylcholine. Methods and resultsTo resolve signals from separate arterioles in a sufficiently large field of view, we developed a method for renal laser speckle contrast imaging. Our setup provides imaging of blood flow in the kidney cortex with a limit of image resolution at 0.8m per pixel and imaging frequency of 160Hz. We used the method to record from 1.5x1.5 mm2 sections of the renal surface in anaesthetised Sprague-Dawley rats in unstimulated conditions and during IV infusion of the vasoconstrictor angiotensin II or the vasodilator acetylcholine. In each section, we resolved and segmented 94.8{+/-}15.66 individual arterioles and venules, and analyzed blood flow using wavelet spectral analysis to identify clusters of synchronized blood vessels. ConclusionsWe observed spatial and temporal evolution of blood vessel clusters of various sizes, including the formation of large (>90 vessels) long-lived clusters (>10 periods) locked at the frequency of the tubular glomerular feedback (TGF) mechanism. The analysis showed that synchronization patterns and thus the co-operative dynamics of nephrons change significantly when either of the vasoactive agents is administered. On average, synchronization was stronger (larger clusters, longer duration) with angiotensin II administration than in the unstimulated state or with acetyl choline. While it weakens with distance, increased synchronization duration spanned the whole field of view, and likely, beyond it. Neighbouring vessels tend to demonstrate in-phase synchronization, especially in the vasoconstricted condition, which is expected to cause locally increased pressure variation. Our results confirm both the presence of the local synchronization in the renal microcirculatory blood flow and the fact that it changes depending on the condition of the vascular network and the blood pressure, which might have further implications for the role of such synchronization in pathologies development.

physiology↗

bioRxiv2021

SERS uncovers the link between conformation of cytochrome c heme and mitochondrial membrane potential

The balance between the mitochondrial respiratory chain activity and the cells needs in ATP ensures optimal cellular function. Cytochrome c is an essential component of the electron transport chain (ETC), which regulates ETC activity, oxygen consumption, ATP synthesis and can initiate apoptosis. The impact of conformational changes in cytochrome c on its function is not understood for lack of access to these changes in intact mitochondria. We have developed a novel sensor that uses unique properties of label-free surface-enhanced Raman spectroscopy (SERS) to identify conformational changes in heme of cytochrome c and to elucidate their role in functioning mitochondria. We verify that molecule bond vibrations assessed by SERS is a reliable indicator of the heme conformation during changes in the inner mitochondrial membrane potential and ETC activity. We have found that cytochrome c heme reversibly switches between planar and ruffled conformations in response to the inner mitochondrial membrane potential and H+ concentration in the intermembrane space to regulate the efficiency of the mitochondrial respiratory chain, thus, adjusting the mitochondrial respiration to the cells consumption of ATP and the overall activity. The ability of the proposed SERS-based sensor to track mitochondrial function opens wide perspectives on cell bioenergetics. For Table of Contents Only O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=127 SRC="FIGDIR/small/425119v2_ufig1.gif" ALT="Figure 1"> View larger version (66K): org.highwire.dtl.DTLVardef@eaaf42org.highwire.dtl.DTLVardef@19826f0org.highwire.dtl.DTLVardef@245e8forg.highwire.dtl.DTLVardef@1bc265d_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗