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Frontiers in Immunology 2024Human Immunodeficiency Virus Type 1 (HIV-1) presents significant challenges to the immune system, predominantly characterized by CD4 T cell depletion, leading to... (Review)
Review
Human Immunodeficiency Virus Type 1 (HIV-1) presents significant challenges to the immune system, predominantly characterized by CD4 T cell depletion, leading to Acquired Immunodeficiency Syndrome (AIDS). Antiretroviral therapy (ART) effectively suppresses the viral load in people with HIV (PWH), leading to a state of chronic infection that is associated with inflammation. This review explores the complex relationship between oxidative phosphorylation, a crucial metabolic pathway for cellular energy production, and HIV-1, emphasizing the dual impact of HIV-1 infection and the metabolic and mitochondrial effects of ART. The review highlights how HIV-1 infection disrupts oxidative phosphorylation, promoting glycolysis and fatty acid synthesis to facilitate viral replication. ART can exacerbate metabolic dysregulation despite controlling viral replication, impacting mitochondrial DNA synthesis and enhancing reactive oxygen species production. These effects collectively contribute to significant changes in oxidative phosphorylation, influencing immune cell metabolism and function. Adenosine triphosphate (ATP) generated through oxidative phosphorylation can influence the metabolic landscape of infected cells through ATP-detected purinergic signaling and contributes to immunometabolic dysfunction. Future research should focus on identifying specific targets within this pathway and exploring the role of purinergic signaling in HIV-1 pathogenesis to enhance HIV-1 treatment modalities, addressing both viral infection and its metabolic consequences.
Topics: Humans; HIV-1; CD4-Positive T-Lymphocytes; Oxidative Phosphorylation; HIV Infections; Adenosine Triphosphate; Immunity
PubMed: 38529284
DOI: 10.3389/fimmu.2024.1360342 -
Pflugers Archiv : European Journal of... Oct 2022Mitochondrial temperature is produced by various metabolic processes inside the mitochondria, particularly oxidative phosphorylation. It was recently reported that... (Review)
Review
Mitochondrial temperature is produced by various metabolic processes inside the mitochondria, particularly oxidative phosphorylation. It was recently reported that mitochondria could normally operate at high temperatures that can reach 50℃. The aim of this review is to identify mitochondrial temperature differences between normal cells and cancer cells. Herein, we discussed the different types of mitochondrial thermosensors and their advantages and disadvantages. We reviewed the studies assessing the mitochondrial temperature in cancer cells and normal cells. We shed the light on the factors involved in maintaining the mitochondrial temperature of normal cells compared to cancer cells.
Topics: Hot Temperature; Mitochondria; Mitochondrial Proteins; Oxidative Phosphorylation; Temperature
PubMed: 35780250
DOI: 10.1007/s00424-022-02719-2 -
Immunology Dec 2022The metabolic reprogramming during T cell activation and differentiation affects T cell fate and immune responses. Cell metabolism may serve as the driving force that... (Review)
Review
The metabolic reprogramming during T cell activation and differentiation affects T cell fate and immune responses. Cell metabolism may serve as the driving force that induces epigenetic modifications, contributing to regulating T cell differentiation. Persistent pathogen infection leads to T cell exhaustion, which is composed of two main subsets and with distinct metabolic characteristics. The progenitor exhausted T cells utilize mitochondrial fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS) for energy, while terminally exhausted T cells mainly rely on glycolytic metabolism with impaired glycolysis and OXPHOS. Here, we compiled the latest research on how T cell metabolism defines differentiation, focusing on T cell exhaustion during chronic infections. In addition, metabolic-related factors including antigen stimulation signals strength, cytokines and epigenetics affecting T cell exhaustion were also reviewed. Furthermore, the intervention strategies on metabolism and epigenetics to reverse T cell exhaustion were discussed in detail, which may contribute to achieving the goal of prevention and treatment of T cell exhaustion.
Topics: T-Lymphocytes; Oxidative Phosphorylation; Glycolysis; Lymphocyte Activation; Cell Differentiation
PubMed: 36088582
DOI: 10.1111/imm.13575 -
Environmental Health Perspectives Jul 1990Uncouplers of oxidative phosphorylation in mitochondria inhibit the coupling between the electron transport and phosphorylation reactions and thus inhibit ATP synthesis... (Review)
Review
Uncouplers of oxidative phosphorylation in mitochondria inhibit the coupling between the electron transport and phosphorylation reactions and thus inhibit ATP synthesis without affecting the respiratory chain and ATP synthase (H(+)-ATPase). Miscellaneous compounds are known to be uncouplers, but weakly acidic uncouplers are representative because they show very potent activities. The most potent uncouplers discovered so far are the hindered phenol SF 6847, and hydrophobic salicylanilide S-13, which are active in vitro at concentrations in the 10 nM range. For induction of uncoupling, an acid dissociable group, bulky hydrophobic moiety and strong electron-withdrawing group are required. Weakly acidic uncouplers are considered to produce uncoupling by their protonophoric action in the H(+)-impermeable mitochondrial membrane. For exerting these effects, the stability of the respective uncoupler anions in the hydrophobic membrane is very important. High stability is achieved by delocalization of the polar ionic charge through uncoupler (chemical)-specific mechanisms. Such an action of weakly acidic uncouplers is characteristic of the highly efficient membrane targeting action of a nonsite-specific type of bioactive compound.
Topics: Acids; Adenosine Triphosphate; Electron Transport; Hydrogen-Ion Concentration; Intracellular Membranes; Membrane Potentials; Mitochondria; Molecular Structure; Oxidative Phosphorylation; Protons; Structure-Activity Relationship; Uncoupling Agents
PubMed: 2176586
DOI: 10.1289/ehp.9087213 -
Cells Oct 2019Cancer development, growth, and metastasis are highly regulated by several transcription regulators (TRs), namely transcription factors, oncogenes, tumor-suppressor... (Review)
Review
Cancer development, growth, and metastasis are highly regulated by several transcription regulators (TRs), namely transcription factors, oncogenes, tumor-suppressor genes, and protein kinases. Although TR roles in these events have been well characterized, their functions in regulating other important cancer cell processes, such as metabolism, have not been systematically examined. In this review, we describe, analyze, and strive to reconstruct the regulatory networks of several TRs acting in the energy metabolism pathways, glycolysis (and its main branching reactions), and oxidative phosphorylation of nonmetastatic and metastatic cancer cells. Moreover, we propose which possible gene targets might allow these TRs to facilitate the modulation of each energy metabolism pathway, depending on the tumor microenvironment.
Topics: Energy Metabolism; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Glycolysis; Humans; Neoplasms; Oxidative Phosphorylation; Tumor Microenvironment
PubMed: 31600993
DOI: 10.3390/cells8101225 -
International Journal of Molecular... Nov 2021The opening of the mitochondrial permeability transition pore (mPTP) has emerged as a pivotal event following traumatic brain injury (TBI). Evidence showing the impact...
The opening of the mitochondrial permeability transition pore (mPTP) has emerged as a pivotal event following traumatic brain injury (TBI). Evidence showing the impact of the translocator protein (TSPO) over mPTP activity has prompted several studies exploring the effect of TSPO ligands, including etifoxine, on the outcome of traumatic brain injury (TBI). Mitochondrial respiration was assessed by respirometry in isolated rat brain mitochondria (RBM) by measurements of oxidative phosphorylation capacity (OXPHOS). The addition of calcium to RBM was used to induce mitochondrial injury and resulted in significant OXPHOS reduction that could be reversed by preincubation of RBM with etifoxine. Sensorimotor and cognitive functions were assessed following controlled cortical impact and compared in vehicle and etifoxine-treated animals. There was no difference between the vehicle and etifoxine groups for sensorimotor functions as assessed by rotarod. In contrast, etifoxine resulted in a significant improvement of cognitive functions expressed by faster recovery in Morris water maze testing. The present findings show a significant neuroprotective effect of etifoxine in TBI through restoration of oxidative phosphorylation capacity associated with improved behavioral and cognitive outcomes. Since etifoxine is a registered drug used in common clinical practice, implementation in a phase II study may represent a reasonable step forward.
Topics: Animals; Anti-Anxiety Agents; Brain Injuries, Traumatic; Cognition; Drug Evaluation, Preclinical; Male; Mitochondria; Oxazines; Oxidative Phosphorylation; Rats, Sprague-Dawley; Rotarod Performance Test; Rats
PubMed: 34884686
DOI: 10.3390/ijms222312881 -
Biochemical Society Transactions Aug 2023While mitochondria oxidative phosphorylation is broadly regulated, the impact of mitochondrial Ca2+ on substrate flux under both physiological and pathological... (Review)
Review
While mitochondria oxidative phosphorylation is broadly regulated, the impact of mitochondrial Ca2+ on substrate flux under both physiological and pathological conditions is increasingly being recognized. Under physiologic conditions, mitochondrial Ca2+ enters through the mitochondrial Ca2+ uniporter and boosts ATP production. However, maintaining Ca2+ homeostasis is crucial as too little Ca2+ inhibits adaptation to stress and Ca2+ overload can trigger cell death. In this review, we discuss new insights obtained over the past several years expanding the relationship between mitochondrial Ca2+ and oxidative phosphorylation, with most data obtained from heart, liver, or skeletal muscle. Two new themes are emerging. First, beyond boosting ATP synthesis, Ca2+ appears to be a critical determinant of fuel substrate choice between glucose and fatty acids. Second, Ca2+ exerts local effects on the electron transport chain indirectly, not via traditional allosteric mechanisms. These depend critically on the transporters involved, such as the uniporter or the Na+-Ca2+ exchanger. Alteration of these new relationships during disease can be either compensatory or harmful and suggest that targeting mitochondrial Ca2+ may be of therapeutic benefit during diseases featuring impairments in oxidative phosphorylation.
Topics: Calcium; Oxidative Phosphorylation; Cell Death; Mitochondria; Adenosine Triphosphate
PubMed: 37641565
DOI: 10.1042/BST20230012 -
Protein & Cell May 2023
Topics: Oxidative Phosphorylation; Acetylglucosamine; Uridine Diphosphate N-Acetylglucosamine
PubMed: 37155316
DOI: 10.1093/procel/pwac009 -
International Journal of Molecular... Apr 2023One important feature of tumour development is the regulatory role of metabolic plasticity in maintaining the balance of mitochondrial oxidative phosphorylation and... (Review)
Review
One important feature of tumour development is the regulatory role of metabolic plasticity in maintaining the balance of mitochondrial oxidative phosphorylation and glycolysis in cancer cells. In recent years, the transition and/or function of metabolic phenotypes between mitochondrial oxidative phosphorylation and glycolysis in tumour cells have been extensively studied. In this review, we aimed to elucidate the characteristics of metabolic plasticity (emphasizing their effects, such as immune escape, angiogenesis migration, invasiveness, heterogeneity, adhesion, and phenotypic properties of cancers, among others) on tumour progression, including the initiation and progression phases. Thus, this article provides an overall understanding of the influence of abnormal metabolic remodeling on malignant proliferation and pathophysiological changes in carcinoma.
Topics: Humans; Oxidative Phosphorylation; Glycolysis; Mitochondria; Cell Transformation, Neoplastic; Carcinoma
PubMed: 37108242
DOI: 10.3390/ijms24087076 -
Frontiers in Immunology 2023The majority of studies on oxidative phosphorylation in immune cells have been performed in mouse models, necessitating human translation. To understand the impact of...
INTRODUCTION
The majority of studies on oxidative phosphorylation in immune cells have been performed in mouse models, necessitating human translation. To understand the impact of oxidative phosphorylation (OXPHOS) deficiency on human immunity, we studied children with primary mitochondrial disease (MtD).
METHODS
scRNAseq analysis of peripheral blood mononuclear cells was performed on matched children with MtD (N = 4) and controls (N = 4). To define B cell function we performed phage display immunoprecipitation sequencing on a cohort of children with MtD (N = 19) and controls (N = 16).
RESULTS
Via scRNAseq, we found marked reductions in select populations involved in the humoral immune response, especially antigen presenting cells, B cell and plasma populations, with sparing of T cell populations. , a marker of bioenergetic stress, was significantly elevated in populations that were most depleted. , a miRNA contained in the intron of , was co-expressed. Knockdown studies of demonstrated its role in promoting survival by modulating apoptosis. To determine the functional consequences of our findings on humoral immunity, we studied the antiviral antibody repertoire in children with MtD and controls using phage display and immunoprecipitation sequencing. Despite similar viral exposomes, MtD displayed antiviral antibodies with less robust fold changes and limited polyclonality.
DISCUSSION
Overall, we show that children with MtD display perturbations in the B cell repertoire which may impact humoral immunity and the ability to clear viral infections.
Topics: Mice; Animals; Child; Humans; Oxidative Phosphorylation; Leukocytes, Mononuclear; Immunity, Humoral; B-Lymphocytes; Antiviral Agents
PubMed: 37483601
DOI: 10.3389/fimmu.2023.1142634