The Integrative Coronary Heart Disease (CHD) Prevention Program
Mark C Houston in The Truth About Heart Disease, 2023
CoQ10 is involved in numerous body functions. It is an antioxidant and is involved in DNA synthesis, lysosomal function, gene expression, mitochondrial protein uncoupling, mitochondrial permeability, mitochondrial ETC (electron transport chain) and ATP production, membrane function, reduction of lipid peroxidation and reduction of oxLDL, apoptosis, and recycling of other micronutrients especially tocopherols and vitamin C. The ETC complex 1–4 on the inner mitochondrial membrane produces ATP via electron transport with CoQ10 involvement particularly at Complex 1 and 2 (Figure 21.4). The electron transport chain of the mitochondria and the production of ATP.
Mitochondrial Dysfunction in Huntington Disease
Abhai Kumar, Debasis Bagchi in Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Mitochondrial dysfunction is a common feature in neurodegenerative disorders as well as aging and other diseases (Velarde 2014). There is sufficient evidence of the association of mitochondrial dysfunction in HD (Petrozzi et al. 2007), usually due to the imbalance of ROS production, changes in the mitochondrial dynamics, the levels/activity of antioxidant defenses, etc. (Sohal and Allen 1990). An overview of mutant HTT (mHTT)-associated mitochondrial dysfunction in HD shown in Figure 9.1. The high energy demands of the neuron are mostly met by mitochondrial OXPHOS as neurons have a limited capacity to utilize energy generated from glycolysis (Herrero-Mendez et al. 2009). Hence, neurons are mostly unprotected to mitochondrial dysfunction. Mitochondrial failure leads to synaptic dysfunction, protein aggregation, brain atrophy, and loss of function (Gonzalez-Lima, Barksdale, Rojas 2014). A recent study showed that mutations in mtDNA at birth can accelerate aging in animals even when the nuclear genomes are normal (Ross et al. 2013), suggesting the involvement of maternally inherited mtDNA variants in age-related disorders. The most important mechanisms associated with mitochondrial anomalies are illustrated in several topics below.
Experimental studies with antioxidants
Ronald R. Watson in NUTRIENTS and FOODS in AIDS, 2017
These are phenolic fat-soluble antioxidants of which the protype member is Coenzyme Q10 (CoQ10). The latter is an important component of the electron transport chain within the mitochondria involved in cellular respiration and ATP generation. Its reduced form (ubiquinol 10) is a powerful membrane antioxidant that can scavenge peroxyl radicals after lipid peroxidation has been initiated. In the inner mitochondrial membrane, Coenzyme Q10 and vitamin E function in a complementary fashion to reduce free radical production.78 Coenzyme Q10 has been extensively studied in patients with heart disease and shown to have benefits in improving cardiac function and survival.79,80 It has been reported by Folkers and colleagues that patients with HIV infection, ARC, and AIDS have decreased levels of CoQ10 in blood compared to healthy subjects.81 The same research group published findings from a small study in healthy volunteers showing improvement in T4/T8 ratios following supplementation with 100 mg/d of CoQ10 over a 2-month period.78 Based on these observations it has been postulated that CoQ10 may have value in ARC or AIDS patients with low T4/T8 ratios. This proposal needs to be put to experimental test.
Identification of Rab7 as an autophagy marker: potential therapeutic approaches and the effect of Qi Teng Xiao Zhuo granule in chronic glomerulonephritis
Published in Pharmaceutical Biology, 2023
Xiujuan Qin, Huiyu Chen, Xiaoli Zhu, Xianjin Xu, Jiarong Gao
Mitochondria are important eukaryotic cell organelles; they produce ATP via oxidative phosphorylation and provide 95% of the cell’s energy requirements. They are also involved in metabolic signal transduction, inflammation, and apoptosis regulation. The kidney is rich in mitochondria, which play a key role in its function, and mitochondrial damage and dysfunction are major factors in many chronic and acute kidney diseases (Tang et al. 2021). Maintaining mitochondrial homeostasis and metabolic balance is crucial for kidney function (Bhargava and Schnellmann 2017). When mitochondrial damage and dysfunction occur, mitophagy is induced to maintain cell homeostasis, removing damaged or excess mitochondria (Su et al. 2023). Transmission electron microscopy showed that abnormal mitochondrial cristae and decreased autophagosomes were apparent in the model group. Interestingly, we also found that mitochondrial damage was reduced after QTXZG treatment.
Understanding the role of cGAS-STING signaling in ischemic stroke: a new avenue for drug discovery
Published in Expert Opinion on Drug Discovery, 2023
Chandan Chauhan, Ravinder Kumar Kaundal
Mitochondrial DNA (mtDNA) is a circular, double-stranded molecule distinct from nuclear DNA. It is inherited solely from the mother [53]. mtDNA contains genes that code for proteins involved in the production of energy & maintaining mitochondria health. mtDNA is vulnerable to oxidative degradation, and as the mitochondrial matrix has an oxidative environment, it is packed into nucleoids. mtDNA functional stability depends on the protein mitochondrial transcription factor-A (TFAM) [54]. TFAM helps in the packaging of mtDNA [52], and loss of TFAM may lead to aberrant mtDNA accumulation in the cytosol [1,55]. Also, the formation of the mitochondrial permeability transition pore (MPTP) has been linked to the leakage of mtDNA and subsequent cGAS-STING signaling mediated immune response [56,57]. Several pathological conditions, including cellular stress or mitochondrial injury, might trigger the release of mtDNA. Lipid excess in the endothelium or Kupffer cells, a critical element in metabolic diseases, may lead to mitochondrial damage and activation of cGAS-STING signaling dependent inflammatory responses [58,59]. Similarly, a high-fat diet-induced adipose inflammation and mitochondrial stress in adipose tissues are linked to mtDNA release into the cytosol, activating the cGAS-STING pathway [60]. Studies reported that oxidized mtDNA produced by NETosis could trigger the cGAS-STING signaling dependent immune response [61]. Blood-brain barrier disruption following thrombolytic therapy in the murine stroke model has been linked to NETosis-induced activation of the cGAS-STING pathway [62].
Syntaphilin mediates axonal growth and synaptic changes through regulation of mitochondrial transport: a potential pharmacological target for neurodegenerative diseases
Published in Journal of Drug Targeting, 2023
Qing-Yun Wu, Hui-Lin Liu, Hai-Yan Wang, Kai-Bin Hu, Ping Liao, Sen Li, Zai-Yun Long, Xiu-Min Lu, Yong-Tang Wang
Physiological activities such as the generation of nerve impulses, the formation of synapses, and the transmission of nerve signalling are all heavily energy-consuming processes. Mitochondria, the organelles found in eukaryotic cells, are responsible for converting stored energy from organic matter into adenosine triphosphate (ATP). They play a critical role in cellular energy metabolism and produce 90% of the ATP required for cellular metabolism [1]. The brain relies heavily on mitochondria to produce most of the ATP needed for its functions and energy metabolism [2], and synapses are the main site of energy expenditure [3]. As the primary energy source for neurons, mitochondria are crucial for maintaining synaptic activities, including synaptic assembly, action potential and synaptic potential production, and synaptic vesicle (SV) transport and recycling [4]. Axonal mitochondrial deficiency affects synaptic transmission, and defective mitochondrial transport and energy deficiency are associated with the failure of axonal regeneration after injury and the pathogenesis of multiple neurological diseases [5–7]. Mitochondrial motility is also affected by stress or damage to its integrity. Consequently, ensuring mitochondrial health and motor function is essential for axonal growth, maintenance of synaptic energy balance, and synaptic function.
Related Knowledge Centers
- Animal
- Cellular Respiration
- Eukaryote
- Lipid Bilayer
- Multicellular Organism
- Red Blood Cell
- Organelle
- Cell
- Adenosine Triphosphate
- Parabasalid