Targeting mitochondrial bioenergetics as a promising therapeutic strategy in metabolic and neurodegenerative diseases

Bhatti, Gurjit Kaur; Gupta, Avdhesh; Pahwa, Paras; Khullar, Naina; Singh, Satwinder; Navik, Umashanker; Kumar, Shashank; Mastana, Sarabjit S.; Reddy, Arubala P.; Reddy, P. Hemachandra; Bhatti, Jasvinder Singh

doi:10.1016/j.bj.2022.05.002

Cited by 19 publications

(17 citation statements)

References 133 publications

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“…Mitochondrial dysfunction, widely observed in ND, contributes to an elevation in oxidative stress and reduction in ATP synthesis, ultimately affecting the anatomy and physiology of neurons followed by neuronal death (Misrani et al, 2021). Therefore, defective mitochondrial bioenergetics play a vital role in inducing ND-associated pathologies (Bhatti et al, 2022).…”

Section: Cellular Bioenergetics Regulationmentioning

confidence: 99%

Resveratrol: A potential therapeutic natural polyphenol for neurodegenerative diseases associated with mitochondrial dysfunction

Yadav

Khan

et al. 2022

Front. Pharmacol.

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Most polyphenols can cross blood-brain barrier, therefore, they are widely utilized in the treatment of various neurodegenerative diseases (ND). Resveratrol, a natural polyphenol contained in blueberry, grapes, mulberry, etc., is well documented to exhibit potent neuroprotective activity against different ND by mitochondria modulation approach. Mitochondrial function impairment is the most common etiology and pathological process in various neurodegenerative disorders, viz. Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis. Nowadays these ND associated with mitochondrial dysfunction have become a major threat to public health as well as health care systems in terms of financial burden. Currently available therapies for ND are limited to symptomatic cures and have inevitable toxic effects. Therefore, there is a strict requirement for a safe and highly effective drug treatment developed from natural compounds. The current review provides updated information about the potential of resveratrol to target mitochondria in the treatment of ND.

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Section: Cellular Bioenergetics Regulationmentioning

confidence: 99%

Resveratrol: A potential therapeutic natural polyphenol for neurodegenerative diseases associated with mitochondrial dysfunction

Yadav

Khan

et al. 2022

Front. Pharmacol.

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“…As the main suborganelles of energy supply, damage to mitochondrial function has a greater impact on tumor cells . Since the mitochondria is the critical suborganelle for ROS production, ROS imbalance of mitochondria can cause fatal outcomes (e.g., ATP supply inhibition, oxidative stress burst induced by REDOX network disorder, mitochondrial DNA mutations, and production of proapoptotic factors), leading to the initiation of apoptosis . Accordingly, the clever combination of different strategies jointly promotes a significant increase in ROS in cells, leading to cell function defects and then apoptosis.…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial Targeted Thermosensitive Nanocarrier for Near-Infrared-Triggered Precise Synergetic Photothermal Nitric Oxide Chemotherapy

Wang,

Zhang,

et al. 2024

ACS Appl. Mater. Interfaces

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Nitric oxide (NO) intervenes, that is, a potential treatment strategy, and has attracted wide attention in the field of tumor therapy. However, the therapeutic effect of NO is still poor, due to its short half-life and instability. Therapeutic concentration ranges of NO should be delivered to the target tissue sites, cell, and even subcellular organelles and to control NO generation. Mitochondria have been considered a major target in cancer therapy for their essential roles in cancer cell metabolism and apoptosis. In this study, mesoporous silicon-coated gold nanorods encapsulated with a mitochondria targeted and the thermosensitive lipid layer (AuNR@MSN-lipid-DOX) served as the carrier to load NO prodrug (BNN6) to build the near-infrared-triggered synergetic photothermal NO-chemotherapy platform (AuNR@MSN(BNN6)-lipid-DOX). The core of AuNR@MSN exhibited excellent photothermal conversion capability and high loading efficiency in terms of BNN6, reaching a high value of 220 mg/g (w/w), which achieved near-infrared-triggered precise release of NO. The outer biocompatible lipid layer, comprising thermosensitive phospholipid DPPC and mitochondrial-targeted DSPE-PEG2000-DOX, guided the whole nanoparticle to the mitochondria of 4T1 cells observed through confocal microscopy. In the mitochondria, the nanoparticles increased the local temperature over 42 °C under NIR irradiation, and a high NO concentration from BNN6 detected by the NO probe and DSPE-PEG2000-DOX significantly inhibited 4T1 cancer cells in vitro and in vivo under the synergetic photothermal therapy (PTT)–NO therapy–chemotherapy modes. The built NIR-triggered combination therapy nanoplatform can serve as a strategy for multimodal collaboration.

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“…In basal conditions, neurons and astrocytes will use the same amount of energy sources. Although neurons synthesize ATP through OXPHOS, astrocytes are specialized in metabolizing glucose through aerobic glycolysis, resulting in an enormous amount of lactate and pyruvate generation from glucose that can be transported to neurons by MCTs and hydrocarboxylic acid receptors 1 (HCAR1) ( Sharma et al, 2019 ; Mani et al, 2021 ; Bhatti et al, 2022 ; Wang et al, 2022c ; Zeviani and Viscomi, 2022 ).…”

Section: Part Ii: Mitochondrial Dysfunction and Its Involvement In Di...mentioning

confidence: 99%

Mitochondria: It is all about energy

et al. 2023

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Mitochondria play a key role in both health and disease. Their function is not limited to energy production but serves multiple mechanisms varying from iron and calcium homeostasis to the production of hormones and neurotransmitters, such as melatonin. They enable and influence communication at all physical levels through interaction with other organelles, the nucleus, and the outside environment. The literature suggests crosstalk mechanisms between mitochondria and circadian clocks, the gut microbiota, and the immune system. They might even be the hub supporting and integrating activity across all these domains. Hence, they might be the (missing) link in both health and disease. Mitochondrial dysfunction is related to metabolic syndrome, neuronal diseases, cancer, cardiovascular and infectious diseases, and inflammatory disorders. In this regard, diseases such as cancer, Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), chronic fatigue syndrome (CFS), and chronic pain are discussed. This review focuses on understanding the mitochondrial mechanisms of action that allow for the maintenance of mitochondrial health and the pathways toward dysregulated mechanisms. Although mitochondria have allowed us to adapt to changes over the course of evolution, in turn, evolution has shaped mitochondria. Each evolution-based intervention influences mitochondria in its own way. The use of physiological stress triggers tolerance to the stressor, achieving adaptability and resistance. This review describes strategies that could recover mitochondrial functioning in multiple diseases, providing a comprehensive, root-cause-focused, integrative approach to recovering health and treating people suffering from chronic diseases.

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Targeting mitochondrial bioenergetics as a promising therapeutic strategy in metabolic and neurodegenerative diseases

Cited by 19 publications

References 133 publications

Resveratrol: A potential therapeutic natural polyphenol for neurodegenerative diseases associated with mitochondrial dysfunction

Resveratrol: A potential therapeutic natural polyphenol for neurodegenerative diseases associated with mitochondrial dysfunction

Mitochondrial Targeted Thermosensitive Nanocarrier for Near-Infrared-Triggered Precise Synergetic Photothermal Nitric Oxide Chemotherapy

Mitochondria: It is all about energy

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