Idebenone Protects Photoreceptors Impaired by Oxidative Phosphorylation Disorder in Retinal Detachment DOI Creative Commons
Li‐Song Wang,

Gaocheng Zou,

Yuanye Yan

et al.

Investigative Ophthalmology & Visual Science, Journal Year: 2025, Volume and Issue: 66(1), P. 17 - 17

Published: Jan. 8, 2025

Purpose: Oxidative phosphorylation (OXPHOS) is an aerobic metabolic mechanism, and its dysfunction plays important role in the pathological changes of ischemic diseases. However, systematic studies on occurrence retinal detachment (RD) are lacking. Methods: Single-cell RNA sequencing (scRNA-seq) human retina was performed to detect various cells after RD. In this study, animal experiments were conducted explore OXPHOS activity addition, idebenone, a coenzyme Q10 (CoQ10) analog currently used treat Leber hereditary optic neuropathy (LHON), improve disorder experimental RD model. Results: ScRNA-seq revealed abnormal energy metabolism pathways Adenosine triphosphate (ATP) reactive oxygen species (ROS) main products OXPHOS, mouse model indicated that rise ROS levels may have greater impact photoreceptors early stage, whereas decreased ATP synthesis observed later stage; these threaten function morphology retina. Idebenone administered mice intragastrically, leading reduced stage post-RD improved which closely related maintenance mitochondrial morphology. Conclusions: leads photoreceptor degeneration RD, can be alleviated by improving function.

Language: Английский

Mitochondrial complex I ROS production and redox signaling in hypoxia DOI Creative Commons
Chidozie Nwabuisi Okoye, Shon A. Koren, Andrew P. Wojtovich

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 67, P. 102926 - 102926

Published: Oct. 16, 2023

Mitochondria are a main source of cellular energy. Oxidative phosphorylation (OXPHOS) is the major process aerobic respiration. Enzyme complexes electron transport chain (ETC) pump protons to generate protonmotive force (Δp) that drives OXPHOS. Complex I an entry point into ETC. oxidizes nicotinamide adenine dinucleotide (NADH) and transfers electrons ubiquinone in reaction coupled with proton pumping. also produces reactive oxygen species (ROS) under various conditions. The enzymatic activities complex can be regulated by metabolic conditions serves as regulatory node ROS plays diverse roles cell metabolism ranging from physiologic pathologic Progress our understanding indicates release important signaling functions. Increasing evidence suggests mismatch energy production demand. In this article, we review role sensing acute hypoxia.

Language: Английский

Citations

102
The neuroprotective effects of targeting key factors of neuronal cell death in neurodegenerative diseases: The role of ER stress, oxidative stress, and neuroinflammation DOI Creative Commons
Mohammad Sobhan Karvandi, Farzam Sheikhzadeh Hesari, Amir Reza Aref

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: March 6, 2023

Neuronal loss is one of the striking causes various central nervous system (CNS) disorders, including major neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), and Amyotrophic lateral sclerosis (ALS). Although these diseases have different features clinical manifestations, they share some common mechanisms pathology. Progressive regional neurons in patients responsible for motor, memory, cognitive dysfunctions, leading to disabilities death. cell death linked pathways conditions. Protein misfolding aggregation, mitochondrial dysfunction, generation reactive oxygen species (ROS), activation innate immune response are most critical hallmarks diseases. Thus, endoplasmic reticulum (ER) stress, oxidative neuroinflammation pathological factors neuronal Even though exact not fully discovered, notable role mentioned well known. On this basis, researchers been prompted investigate neuroprotective effects targeting underlying determine a promising therapeutic approach treatment. This review provides an overview ER death, mainly discussing or molecules involved factors.

Language: Английский

Citations

47
Mitochondrial disorders leading to Alzheimer’s disease—perspectives of diagnosis and treatment DOI Creative Commons
Magdalena Pszczołowska,

Kamil Walczak,

Weronika Miśków

et al.

GeroScience, Journal Year: 2024, Volume and Issue: 46(3), P. 2977 - 2988

Published: March 8, 2024

Abstract Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common cause of dementia globally. The pathogenesis AD remains still unclear. three main features are extracellular deposits amyloid beta (Aβ) plaque, accumulation abnormal formation hyper-phosphorylated tau protein, neuronal loss. Mitochondrial impairment plays an important role in AD. There problems with decreased activity multiple complexes, disturbed mitochondrial fusion, fission or reactive oxygen species (ROS). Moreover, transport impaired Mouse models many research show disruptions anterograde retrograde transport. Both transportation network have huge impact on synapse loss and, as result, cognitive impairment. One very serious also disruption insulin signaling which impairs Aβ removal. Discovering precise mechanisms leading to enables us find new treatment possibilities. Recent studies indicate positive influence metformin antioxidants such MitoQ, SS-31, SkQ, MitoApo, MitoTEMPO, MitoVitE functioning hence prevent decline. Impairments may be treated division inhibitor-1 ceramide. Graphical (Graphic content via Canva Pro)

Language: Английский

Citations

17
Advances in Alzheimer's disease: A multifaceted review of potential therapies and diagnostic techniques for early detection DOI
Monika Sharma, Pankaj Pal, Sukesh Kumar Gupta

et al.

Neurochemistry International, Journal Year: 2024, Volume and Issue: 177, P. 105761 - 105761

Published: May 7, 2024

Language: Английский

Citations

16
Cognitive dysfunction in diabetes: abnormal glucose metabolic regulation in the brain DOI Creative Commons
Shan Zhang, Yueying Zhang,

Zhige Wen

et al.

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: June 16, 2023

Cognitive dysfunction is increasingly recognized as a complication and comorbidity of diabetes, supported by evidence abnormal brain structure function. Although few mechanistic metabolic studies have shown clear pathophysiological links between diabetes cognitive dysfunction, there are several plausible ways in which this connection may occur. Since, functions require constant supply glucose an energy source, the be more susceptible to abnormalities metabolism. Glucose under diabetic conditions play important role affecting transport reducing These changes, along with oxidative stress, inflammation, mitochondrial other factors, can affect synaptic transmission, neural plasticity, ultimately lead impaired neuronal Insulin signal triggers intracellular transduction that regulates resistance, one hallmark has also been linked cerebral metabolism brain. In review, we conclude critical alterations underlying (DCD), associated multiple pathogenic factors such others. Brain insulin resistance highly emphasized characterized mechanism DCD.

Language: Английский

Citations

40
Mitochondria as intracellular signalling organelles. An update DOI Creative Commons
Lucia‐Doina Popov

Cellular Signalling, Journal Year: 2023, Volume and Issue: 109, P. 110794 - 110794

Published: July 6, 2023

Traditionally, mitochondria are known as "the powerhouse of the cell," responsible for energy (ATP) generation (by electron transport chain, oxidative phosphorylation, tricarboxylic acid cycle, and fatty ß-oxidation), regulation several metabolic processes, including redox homeostasis, calcium signalling, cellular apoptosis. The extensive studies conducted in last decades portray multifaceted signalling organelles that ultimately command cells' survival or death. Based on current knowledge, we'll outline mitochondrial to other intracellular compartments homeostasis pathology-related stress conditions here. following topics discussed: (i) mtROS mitohormesis, (ii) Ca2+ signalling; (iii) anterograde (nucleus-to-mitochondria) retrograde (mitochondria-to-nucleus) signal transduction, (iv) mtDNA role immunity inflammation, (v) induction mitophagy- apoptosis - cascades, (vi) dysfunctions (mitochondriopathies) cardiovascular, neurodegenerative, malignant diseases. novel insights into molecular mechanisms mitochondria-mediated can explain adaptation environmental stresses achieve cell survival.

Language: Английский

Citations

30
Sirtuin-3 activates the mitochondrial unfolded protein response and reduces cerebral ischemia/reperfusion injury DOI Creative Commons
Xiaowei Xie, Xu Qian,

Zhou Dingzhou

et al.

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(13), P. 4327 - 4339

Published: Jan. 1, 2023

Sirtuin-3 (Sirt3) deacetylates several mitochondrial proteins implicated into cerebral ischemia/reperfusion (I/R) injury. The unfolded protein response (UPRmt) favors proteostasis during various stressors. Here, we used Sirt3 transgenic mice and a transient middle artery occlusion model to evaluate the molecular basis of on UPRmt brain post-ischemic dysfunction. present study illustrated that abundance was suppressed in after ischemic abnormalities. Overexpression vivo infarction size attenuated neuroinflammation I/R overexpression restored neural viability by reducing ROS synthesis, maintaining potential improving adenosine triphosphate synthesis. protected neuronal mitochondria against malfunction via eliciting forkhead box O3 (Foxo3)/sphingosine kinase 1 (Sphk1) pathway. Inhibiting either or Foxo3/Sphk1 pathway relieved favorable influence function behavior. In contrast, Sphk1 sufficient reduce size, attenuate neuroinflammation, sustain prevent abnormalities post-ischemia Thus, protects homeostasis, Sirt3/Foxo3/Sphk1 is promosing therapeutic candidate for stroke.

Language: Английский

Citations

28
The Role of PGC-1α-Mediated Mitochondrial Biogenesis in Neurons DOI
Mengjie Chen,

Ru-Yu Yan,

Jian-Sheng Luo

et al.

Neurochemical Research, Journal Year: 2023, Volume and Issue: 48(9), P. 2595 - 2606

Published: April 25, 2023

Language: Английский

Citations

27
Maintenance of mitochondrial homeostasis for Alzheimer's disease: Strategies and challenges DOI Creative Commons
Ying Han,

Daozhou Liu,

Ying Cheng

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 63, P. 102734 - 102734

Published: May 6, 2023

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, and its early onset closely related to mitochondrial energy metabolism. The brain only 2% body weight, but consumes 20% total needs. Mitochondria are responsible for providing in cells, maintaining their homeostasis ensures an adequate supply brain. Mitochondrial constituted by quantity quality control, which dynamically regulated metabolism, dynamics control. Impaired metabolism cells occurs AD, a promising therapeutic target future. We summarized mechanism influence on pathogenesis strategies homeostasis, targeting strategies. This review concludes with authors' opinions future research development AD.

Language: Английский

Citations

23
Ovarian aging: energy metabolism of oocytes DOI Creative Commons
Shenglan Bao, Tailang Yin,

Su Liu

et al.

Journal of Ovarian Research, Journal Year: 2024, Volume and Issue: 17(1)

Published: May 31, 2024

Abstract In women who are getting older, the quantity and quality of their follicles or oocytes decline. This is characterized by decreased ovarian reserve function (DOR), fewer remaining oocytes, lower oocytes. As more choose to delay childbirth, decline in fertility associated with age has become a significant concern for modern women. The oocyte key indicator aging. Many studies suggest that age-related changes energy metabolism may impact quality. Changes affect adenosine 5'-triphosphate (ATP) production, but how related products proteins influence remains largely unknown. review focuses on aging its potential quality, as well therapeutic strategies partially metabolism. research aims enhance our understanding metabolism, identification biomarkers treatment methods.

Language: Английский

Citations

14