Modulation of Nrf2 and Mitochondrial Function: Pharmacological Implications

Mammalians are constantly exposed to exogenous and endogenous sources of free radicals that have both favorable and harmful effects on the cellular systems. Oxidative stress (OS) is an imbalance of reactive oxygen species (ROS) and antioxidants in the body that can lead to serious cell damage. It is associated with many diseases such as cancer, Alzheimer’s disease and heart disease. Background/Objectives: The Nuclear factor-2 erythroid-related factor-2 (Nrf2) is a transcription factor that controls the cellular oxidation state using antioxidant systems in the body and affects mitochondrial activities. Increased Nrf2 levels serve to protect cells from mitochondrial toxins; however, Nrf2 activity is inhibited in mitochondria-related diseases. In addition, Nrf2 is involved in mitochondrial activities for OS control. Methods: As mitochondrial wellbeing and activity is the chief controller for cellular metabolism, Nrf2 is a critical regulator for metabolic pathways. Thus, Nrf2 is the chief organizer of protection against OS in the cells. Nrf2 activator molecules support mitochondrial activity by stimulating mitophagy and helping to battle OS-related permeability transition. Conclusions: This review describes the influence of Nrf2 on OS and the way Nrf2 modulates mitochondrial function. Furthermore, we highlight recent studies of Nrf2 regarding its possible role in cell systems as well as pharmacological implications. Furthermore, this review emphasizes the importance of the mitochondria in the development of life-threatening diseases; pharmacological activation of Nrf2 is an important strategy to counter mitochondrial dysfunction

• Publication year

  2025

• Venue

  Pharmaceuticals

• Publication date

  2025-11-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.3390/ph18111698PMID 41304943PMCID 12655643
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Luteolin: A potential therapeutic agent for respiratory diseases.

  2025cited by this paper
• Mitochondrial metabolism and cancer therapeutic innovation

  2025cited by this paper
• The Nrf2-Related Pathways and the Antiandrogenic Effects Are Enhanced In Vitro and In Silico by the Combination of Graminex®G96® Pollen and Teupol 25P in Cell Models of Benign Prostate Hyperplasia

  2025cited by this paper
• A Natural Compound Methylnissolin: Physicochemical Properties, Pharmacological Activities, Pharmacokinetics and Resource Development

  2025cited by this paper
• Neuroprotective potential of epigallocatechin gallate in Neurodegenerative Diseases: Insights into molecular mechanisms and clinical Relevance.

  2025cited by this paper
• Flavonoids and their role in oxidative stress, inflammation, and human diseases.

  2025cited by this paper
• Dioscin regulates oxidative stress and autophagy in uric acid-induced HK-2 cells through the P62-KEAP1-NRF2 signaling pathway

  2025cited by this paper
• Hinokitiol Modulates Nrf2/HO-1 Signaling, Autophagy, and URAT1 in Hyperuricemia and Oxidative Stress Models of Renal Injury.

  2025cited by this paper
• Baicalein-mediated regulation of Nrf2/ARE, NFĸB, and MAPK signaling in Huntington’s disease: a promising strategy against neuroinflammation and neurodegeneration

  2025cited by this paper
• Nrf2 as a regulator of energy metabolism and mitochondrial function

  2024cited by this paper
• The Role of Nrf2 in the Regulation of Mitochondrial Function and Ferroptosis in Pancreatic Cancer

  2024cited by this paper
• Modulation of NRF2/KEAP1 Signaling by Phytotherapeutics in Periodontitis

  2024cited by this paper
• Unveiling a novel signalling pathway involving NRF2 and PGAM5 in regulating the mitochondrial unfolded protein response in stressed cardiomyocytes.

  2024cited by this paper
• Regulation of Keap1-Nrf2 signaling in health and diseases

  2024cited by this paper
• Keap1-Nrf2 pathway: a key mechanism in the occurrence and development of cancer

  2024cited by this paper
• The role of Nrf2 signaling pathways in nerve damage repair.

  2024cited by this paper
• Editorial: Mitochondrial bioenergetics and metabolism: implication for human health and disease

  2024cited by this paper
• Protein-rich foods, sea foods, and gut microbiota amplify immune responses in chronic diseases and cancers - Targeting PERK as a novel therapeutic strategy for chronic inflammatory diseases, neurodegenerative disorders, and cancer.

  2024cited by this paper
• NRF2 inhibitors: Recent progress, future design and therapeutic potential.

  2024cited by this paper
• Mitochondrial bioenergetics of breast cancer.

  2024cited by this paper
• Sulforaphane upregulates the mRNA expression of NRF2 and NQO1 in non-dialysis patients with chronic kidney disease.

  2024cited by this paper
• Mechanism of Action and Related Natural Regulators of Nrf2 in Nonalcoholic Fatty Liver Disease.

  2023cited by this paper
• The KEAP1-NRF2 System and Neurodegenerative Diseases

  2023cited by this paper
• The Roles of NFR2-Regulated Oxidative Stress and Mitochondrial Quality Control in Chronic Liver Diseases

  2023cited by this paper
• A Review of the Potential of Nuclear Factor [Erythroid-Derived 2]-like 2 Activation in Autoimmune Diseases

  2023cited by this paper
• Modulation of NRF2: Biological Dualism in Cancer, Targets and Possible Therapeutic Applications

  2023cited by this paper
• Maternal zinc alleviates tert-butyl hydroperoxide-induced mitochondrial oxidative stress on embryonic development involving the activation of Nrf2/PGC-1α pathway

  2023cited by this paper
• α‐Mangostin induces oxidative damage, mitochondrial dysfunction, and apoptosis in a triple‐negative breast cancer model

  2023cited by this paper
• NRF2: New Mechanistic Insights and Therapeutic Perspectives

  2023cited by this paper
• Metabolic reprogramming in cancer: Mechanisms and therapeutics

  2023cited by this paper
• The Key Role of Mitochondrial Function in Health and Disease

  2023cited by this paper
• Antioxidants attenuate mitochondrial oxidative damage through the Nrf2 pathway: A promising therapeutic strategy for stroke

  2023cited by this paper
• Mitochondrial dynamics in health and disease: mechanisms and potential targets

  2023cited by this paper
• Mitochondrial complex I ROS production and redox signaling in hypoxia

  2023cited by this paper
• The Multi-Faceted Consequences of NRF2 Activation throughout Carcinogenesis

  2023cited by this paper
• Melatonin as mitochondria-targeted drug.

  2023cited by this paper
• Transcription Factor Nrf2 and Mitochondria – Friends or Foes in the Regulation of Aging Rate

  2022cited by this paper
• Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease

  2022cited by this paper
• Dimethyl fumarate: A review of preclinical efficacy in models of neurodegenerative diseases.

  2022cited by this paper
• The PERKs of mitochondria protection during stress: insights for PERK modulation in neurodegenerative and metabolic diseases

  2022cited by this paper
• Mitochondrial autophagy: molecular mechanisms and implications for cardiovascular disease

  2022cited by this paper
• Dimethyl Fumarate Triggers the Antioxidant Defense System in Human Retinal Endothelial Cells through Nrf2 Activation

  2022cited by this paper
• Targeting mitochondrial bioenergetics as a promising therapeutic strategy in metabolic and neurodegenerative diseases

  2022cited by this paper
• Natural and Synthetic Xanthone Derivatives Counteract Oxidative Stress via Nrf2 Modulation in Inflamed Human Macrophages

  2022cited by this paper
• Mitochondrial ROS, ER Stress, and Nrf2 Crosstalk in the Regulation of Mitochondrial Apoptosis Induced by Arsenite

  2022cited by this paper
• Platinum-based nanocomposites loaded with MTH1 inhibitor amplify oxidative damage for cancer therapy.

  2022cited by this paper
• A Perspective on Nrf2 Signaling Pathway for Neuroinflammation: A Potential Therapeutic Target in Alzheimer's and Parkinson's Diseases

  2022cited by this paper
• NRF2 and Mitochondrial Function in Cancer and Cancer Stem Cells

  2022cited by this paper
• NRF2: A crucial regulator for mitochondrial metabolic shift and prostate cancer progression

  2022cited by this paper
• Mitochondrial DNA Repair in Neurodegenerative Diseases and Ageing

  2022cited by this paper
• Melatonin and redox homeostasis

  2022cited by this paper
• Mechanisms of mitochondrial respiratory adaptation

  2022cited by this paper
• Mechanisms and mathematical modelling of ROS production by the mitochondrial electron transport chain.

  2022cited by this paper
• Defining roles of specific reactive oxygen species (ROS) in cell biology and physiology

  2022cited by this paper
• A Pivotal Role of Nrf2 in Neurodegenerative Disorders: A New Way for Therapeutic Strategies

  2022cited by this paper
• NRF2/PGC-1α-mediated mitochondrial biogenesis contributes to T-2 toxin-induced toxicity in human neuroblastoma SH-SY5Y cells.

  2022cited by this paper
• Mitochondria-targeted nanozymes eliminate oxidative damage in retinal neovascularization disease.

  2022cited by this paper
• The Uncoupling Proteins: A Systematic Review on the Mechanism Used in the Prevention of Oxidative Stress

  2022cited by this paper
• Nrf2 as a regulator of mitochondrial function: Energy metabolism and beyond.

  2022cited by this paper
• The Role of NRF2/KEAP1 Signaling Pathway in Cancer Metabolism

  2021cited by this paper
• Bardoxolone and bardoxolone methyl, two Nrf2 activators in clinical trials, inhibit SARS-CoV-2 replication and its 3C-like protease

  2021cited by this paper
• Cancer cell metabolic plasticity in migration and metastasis

  2021cited by this paper
• Effects of acute iron overload on Nrf2-related glutathione metabolism in rat brain

  2021cited by this paper
• Enzymatic and Non-Enzymatic Molecules with Antioxidant Function

  2021cited by this paper
• Mitochondrial Management of Reactive Oxygen Species

  2021cited by this paper
• Nuclear Factor Erythroid-2-Related Factor 2 Signaling in the Neuropathophysiology of Inherited Metabolic Disorders

  2021cited by this paper
• The mitochondrial thioredoxin reductase system (TrxR2) in vascular endothelium controls peroxynitrite levels and tissue integrity

  2021cited by this paper
• The Interplay Between Mitochondrial Reactive Oxygen Species, Endoplasmic Reticulum Stress, and Nrf2 Signaling in Cardiometabolic Health

  2021cited by this paper
• Are mitochondria the main contributor of reactive oxygen species in cells?

  2021cited by this paper
• Contribution of the Nrf2 Pathway on Oxidative Damage and Mitochondrial Failure in Parkinson and Alzheimer’s Disease

  2021cited by this paper
• The Effects of Two Nrf2 Activators, Bardoxolone Methyl and Omaveloxolone, on Retinal Ganglion Cell Survival during Ischemic Optic Neuropathy

  2021cited by this paper
• A novel role of KEAP1/PGAM5 complex: ROS sensor for inducing mitophagy

  2021cited by this paper
• Therapeutic Targeting of the NRF2 Signaling Pathway in Cancer

  2021cited by this paper
• Mitochondrial Structure and Bioenergetics in Normal and Disease Conditions

  2021cited by this paper
• Targeting oxidative stress in disease: promise and limitations of antioxidant therapy

  2021cited by this paper
• Reactive Oxygen Species/Reactive Nitrogen Species as Messengers in the Gut: Impact on Physiology and Metabolic Disorders

  2021cited by this paper
• Metabolic Adaptations in Cancer Stem Cells

  2020cited by this paper
• Regulation of Nrf2 by Mitochondrial Reactive Oxygen Species in Physiology and Pathology

  2020cited by this paper
• Transcriptional activation of antioxidant gene expression by Nrf2 protects against mitochondrial dysfunction and neuronal death associated with acute and chronic neurodegeneration.

  2020cited by this paper
• Nrf2 is activated by disruption of mitochondrial thiol homeostasis but not by enhanced mitochondrial superoxide production

  2020cited by this paper
• The basics of mitochondrial cAMP signalling: Where, when, why.

  2020cited by this paper
• Roles and Functions of ROS and RNS in Cellular Physiology and Pathology

  2020cited by this paper
• Promotion of Mitochondrial Protection by Emodin in Methylglyoxal-Treated Human Neuroblastoma SH-SY5Y Cells: Involvement of the AMPK/Nrf2/HO-1 Axis

  2020cited by this paper
• Serum irisin levels are decreased in patients with sepsis, and exogenous irisin suppresses ferroptosis in the liver of septic mice

  2020cited by this paper
• Nuclear Factor-Erythroid 2-Related Factor 2 (Nrf2) and Mitochondrial Dynamics/Mitophagy in Neurological Diseases

  2020cited by this paper
• Mitophagy Receptors and Mediators: Therapeutic Targets in the Management of Cardiovascular Ageing.

  2020cited by this paper
• Mitochondrial Reactive Oxygen Species: Double-Edged Weapon in Host Defense and Pathological Inflammation During Infection

  2020cited by this paper
• PHB2 (prohibitin 2) promotes PINK1-PRKN/Parkin-dependent mitophagy by the PARL-PGAM5-PINK1 axis

  2020cited by this paper
• Oxidative Stress Modulation by Cameroonian Spice Extracts in HepG2 Cells: Involvement of Nrf2 and Improvement of Glucose Uptake

  2020cited by this paper
• Blackout in the powerhouse: clinical phenotypes associated with defects in the assembly of OXPHOS complexes and the mitoribosome

  2020cited by this paper
• Sulforaphane as an anticancer molecule: mechanisms of action, synergistic effects, enhancement of drug safety, and delivery systems

  2020cited by this paper
• Disruption of the Keap1/Nrf2-Antioxidant Response System After Chronic Doxorubicin Exposure In Vivo

  2020cited by this paper
• Neuroprotective role of glutathione peroxidase 4 in experimental subarachnoid hemorrhage models.

  2020cited by this paper
• Outstanding Questions in Mitophagy: What we Do and Do Not Know.

  2020cited by this paper
• Studies on characteristics and anti-diabetic and -nephritic effects of polysaccharides isolated from Paecilomyces hepiali fermentation mycelium in db/db mice.

  2020cited by this paper
• The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies

  2020cited by this paper
• Neuronal mitochondria-targeted therapy for Alzheimer’s disease by systemic delivery of resveratrol using dual-modified novel biomimetic nanosystems

  2020cited by this paper
• NRF2, a Transcription Factor for Stress Response and Beyond

  2020cited by this paper
• Contribution of Nrf2 Modulation to the Mechanism of Action of Analgesic and Anti-inflammatory Drugs in Pre-clinical and Clinical Stages

  2019cited by this paper
• An old medicine as a new drug to prevent mitochondrial complex I from producing oxygen radicals

  2019cited by this paper

• No citing papers are available for this paper.