bims-cytox1 2024-01-28 papers

Issue of 2024‒01‒28
four papers selected by
Gavin McStay, Liverpool John Moores University

Antioxidants (Basel). 2023 Dec 21. pii: 19. [Epub ahead of print]13(1):

High Sucrose Diet-Induced Subunit I Tyrosine 304 Phosphorylation of Cytochrome c Oxidase Leads to Liver Mitochondrial Respiratory Dysfunction in the Cohen Diabetic Rat Model.

Tasnim Arroum, Lucynda Pham, Taryn E Raisanen, Paul T Morse, Junmei Wan, Jamie Bell, Rachel Lax, Ann Saada, Maik Hüttemann, Sarah Weksler-Zangen.

The mitochondrial oxidative phosphorylation process generates most of the cellular energy and free radicals in mammalian tissues. Both factors play a critical role in numerous human diseases that could be affected by reversible phosphorylation events that regulate the function and activity of the oxidative phosphorylation complexes. In this study, we analyzed liver mitochondria of Cohen diabetes-sensitive (CDs) and Cohen diabetes-resistant (CDr) rats, using blue native gel electrophoresis (BN-PAGE) in combination with mitochondrial activity measurements and a site-specific tyrosine phosphorylation implicated in inflammation, a known driver of diabetes pathology. We uncovered the presence of a specific inhibitory phosphorylation on tyrosine 304 of catalytic subunit I of dimeric cytochrome c oxidase (CcO, complex IV). Driven by a high sucrose diet in both CDr and CDs rats, Y304 phosphorylation, which occurs close to the catalytic oxygen binding site, correlates with a decrease in CcO activity and respiratory dysfunction in rat liver tissue under hyperglycemic conditions. We propose that this phosphorylation, specifically seen in dimeric CcO and induced by high sucrose diet-mediated inflammatory signaling, triggers enzymatic activity decline of complex IV dimers and the assembly of supercomplexes in liver tissue as a molecular mechanism underlying a (pre-)diabetic phenotype.

Keywords: Cohen diabetic rat; blue native gel; cytochrome c oxidase; dimeric complex IV; high sucrose diet; inflammation; inhibitory phosphorylation; liver mitochondria; mitochondria; mitochondrial dysfunction; respiratory dysfunction; type 2 diabetes; tyrosine 304 CcO subunit I; tyrosine phosphorylation

DOI: https://doi.org/10.3390/antiox13010019

Pharmacol Biochem Behav. 2024 Jan 18. pii: S0091-3057(24)00003-0. [Epub ahead of print]236 173709

Physical activity as a promoter of stress resilience: An analysis of behavioral effects and brain connectivity with cytochrome c-oxidase activity in adult male Wistar rats.

Azucena Begega, Matías López, Ignacio Cuesta-López, Claudia I Jove, Marcelino Cuesta Izquierdo.

Physical activity (PA) is very beneficial for physical and mental health. This study aims to examine the resilience-inducting effect of PA in adult male Wistar rats exposed to unpredictable chronic mild stress (UCMS). Furthermore, we analyzed the influence of PA on behavioral tasks and functional brain connectivity with cytochrome c oxidase technique. The cytochrome c oxidase (CCO) is a mitochondrial enzyme involved in oxidative phosphorylation and ATP generation. For this analysis, we included five groups: Basal (n = 10, to determine the basal level of brain activity), Behav (n = 15, subjected exclusively to behavioral tests), PA (n = 10, exposed to physical activity), UCMS (n = 15, subjected to a stress protocol) and PA + UCMS (n = 15, exposed to PA prior to stress). The UCMS protocol consisted of randomly presenting several different stressors over four consecutive weeks. We evaluated several behaviors of the Behav, UCMS, and PA + UCMS groups. This assessment includes the hedonic responses using the sucrose consumption task, unconditioned anxiety with the zero maze, and coping strategies assessed with the cat odor test. The UCMS group showed an anhedonia profile and increased anxiety compared with the other groups. Although in the exposure to cat odor test, the PA + UCMS remained for the same time in the cat odor compartment as the other groups, it did not approach the odor, showing that it detected the risk. This response is more adaptive than the responses of the UCMS and Behav groups. An exploratory analysis of the cerebral connections showed an increase in CCO activity in the UCMS group compared to the other groups. This overactivity was reduced in dorsal Cornu Ammonis 3(dCA3) by prior PA. In this region, PA + UCMS showed similar activity as the groups not subjected to chronic stress. Therefore, PA can prevent the harmful effects of chronic stress on dCA3.

Keywords: Cerebral networks; Cytochrome c oxidase; Physical activity; Rats; Resilience

DOI: https://doi.org/10.1016/j.pbb.2024.173709

J Biomed Opt. 2024 Jan;29(1): 015002

HyperTRCSS: A hyperspectral time-resolved compressive sensing spectrometer for depth-sensitive monitoring of cytochrome-c-oxidase and blood oxygenation.

Natalie C Li, Seva Ioussoufovitch, Mamadou Diop.

Significance: Hyperspectral time-resolved (TR) near-infrared spectroscopy offers the potential to monitor cytochrome-c-oxidase (oxCCO) and blood oxygenation in the adult brain with minimal scalp/skull contamination. We introduce a hyperspectral TR spectrometer that uses compressive sensing to minimize acquisition time without compromising spectral range or resolution and demonstrate oxCCO and blood oxygenation monitoring in deep tissue.Aim: Develop a hyperspectral TR compressive sensing spectrometer and use it to monitor oxCCO and blood oxygenation in deep tissue.
Approach: Homogeneous tissue-mimicking phantom experiments were conducted to confirm the spectrometer's sensitivity to oxCCO and blood oxygenation. Two-layer phantoms were used to evaluate the spectrometer's sensitivity to oxCCO and blood oxygenation in the bottom layer through a 10 mm thick static top layer.
Results: The spectrometer was sensitive to oxCCO and blood oxygenation changes in the bottom layer of the two-layer phantoms, as confirmed by concomitant measurements acquired directly from the bottom layer. Measures of oxCCO and blood oxygenation by the spectrometer were highly correlated with "gold standard" measures in the homogeneous and two-layer phantom experiments.
Conclusions: The results show that the hyperspectral TR compressive sensing spectrometer is sensitive to changes in oxCCO and blood oxygenation in deep tissue through a thick static top layer.

Keywords: blood-yeast phantom; cytochrome-c-oxidase; hyperspectral; near-infrared spectroscopy; time-resolved

DOI: https://doi.org/10.1117/1.JBO.29.1.015002

Neurotherapeutics. 2024 Jan 19. pii: S1878-7479(24)00009-6. [Epub ahead of print]21(1): e00323

Applications of near-infrared spectroscopy in epilepsy, with a focus on mitochondrial disorders.

Kosar Khaksari, Wei-Liang Chen, Mongkol Chanvanichtrakool, Alexa Taylor, Rohan Kotla, Andrea L Gropman.

Mitochondrial diseases are inherited disorders that impede the mitochondria's ability to produce sufficient energy for the cells. They can affect different parts of the body, notably the brain. Neurological symptoms and epilepsy are prevalent in patients with mitochondrial disorders. The epileptogenicity of mitochondrial disorder is a complex process involving the intricate interplay between abnormal energy metabolism and neuronal activity. Several modalities have been used to detect seizures in different disorders including mitochondrial disorders. EEG serve as the gold standard for diagnosis and localization, commonly complemented by additional imaging modalities to enhance source localization. In the current work, we propose the use of functional near-infrared spectroscopy (fNIRS) to identify the occurrence of epilepsy and seizure in patients with mitochondrial disorders. fNIRS proves an advantageous imaging technique due to its portability and insensitivity to motion especially for imaging infants and children. It has added a valuable factor to our understanding of energy metabolism and neuronal activity. Its real-time monitoring with high spatial resolution supplements traditional diagnostic tools such as EEG and provides a comprehensive understanding of seizure and epileptogenesis. The utility of fNIRS extends to its ability to detect changes in Cytochrome c oxidase (CcO) which is a crucial enzyme in cellular respiration. This facet enhances our insight into the metabolic dimension of epilepsy related to mitochondrial dysfunction. By providing valuable insights into both energy metabolism and neuronal activity, fNIRS emerges as a promising imaging technique for unveiling the complexities of mitochondrial disorders and their neurological manifestations.

Keywords: Brain biomarkers; Epilepsy; Mitochondrial disease; Near-infrared spectroscopy; Neuromonitoring; Seizure

DOI: https://doi.org/10.1016/j.neurot.2024.e00323