Abstract
The apoptosis inducing factor (AIF) was first discovered as a caspase-independent apoptosis effector that promoted cell death upon release from the mitochondria (triggered by pro-apoptotic stimuli) and relocalization into the nucleus, where it promotes chromatin condensation and DNA fragmentation. AIF is a mammalian mitochondrial FAD-dependent flavoenzyme, ubiquitous in vertebrate cells, and with orthologs in all eukaryotes. Beyond its role in apoptosis AIF has additional functions in mitochondria, mainly related with the redox function of its flavin adenine dinucleotide cofactor (FAD), which despite being poorly understood are vital. Thus, defects in AIF trigger major dysfunctions in oxidative phosphorylation, and cause severe illnesses related with neurodegeneration as a consequence of mitochondriopathies. AIF folds in three modules: a FAD-binding, a nicotine adenine dinucleotide (NADH)-binding and a C-terminal modules. Upon reduction of the flavin cofactor by NADH, conformational changes leading to AIF dimerization are proposed as a key early event in the mitochondrial sensing/signaling functions of AIF. The recent interest in the design of new therapies to modulate caspase-independent apoptosis pathways also makes AIF a potential pharmacological target to treat pathological disorders related with AIF dependent mitochondriopathies. Therefore, the first step in this direction must be to understand the molecular basis of the AIF redox reactions and their relationship with the apoptotic function. Here, we examine recent research towards the molecular mechanisms linked to the AIF oxido-reduction properties.
Keywords: Apoptosis inducing factor, NADH-reductase activity, programmed cell death, mitochondrial respiration, nucleus
Current Pharmaceutical Design
Title:The Oxido-reductase Activity of the Apoptosis Inducing Factor: A Promising Pharmacological Tool?
Volume: 19 Issue: 14
Author(s): Patricia Ferreira, Raquel Villanueva, Lauriane Cabon, Santos A. Susin and Milagros Medina
Affiliation:
Keywords: Apoptosis inducing factor, NADH-reductase activity, programmed cell death, mitochondrial respiration, nucleus
Abstract: The apoptosis inducing factor (AIF) was first discovered as a caspase-independent apoptosis effector that promoted cell death upon release from the mitochondria (triggered by pro-apoptotic stimuli) and relocalization into the nucleus, where it promotes chromatin condensation and DNA fragmentation. AIF is a mammalian mitochondrial FAD-dependent flavoenzyme, ubiquitous in vertebrate cells, and with orthologs in all eukaryotes. Beyond its role in apoptosis AIF has additional functions in mitochondria, mainly related with the redox function of its flavin adenine dinucleotide cofactor (FAD), which despite being poorly understood are vital. Thus, defects in AIF trigger major dysfunctions in oxidative phosphorylation, and cause severe illnesses related with neurodegeneration as a consequence of mitochondriopathies. AIF folds in three modules: a FAD-binding, a nicotine adenine dinucleotide (NADH)-binding and a C-terminal modules. Upon reduction of the flavin cofactor by NADH, conformational changes leading to AIF dimerization are proposed as a key early event in the mitochondrial sensing/signaling functions of AIF. The recent interest in the design of new therapies to modulate caspase-independent apoptosis pathways also makes AIF a potential pharmacological target to treat pathological disorders related with AIF dependent mitochondriopathies. Therefore, the first step in this direction must be to understand the molecular basis of the AIF redox reactions and their relationship with the apoptotic function. Here, we examine recent research towards the molecular mechanisms linked to the AIF oxido-reduction properties.
Export Options
About this article
Cite this article as:
Ferreira Patricia, Villanueva Raquel, Cabon Lauriane, A. Susin Santos and Medina Milagros, The Oxido-reductase Activity of the Apoptosis Inducing Factor: A Promising Pharmacological Tool?, Current Pharmaceutical Design 2013; 19 (14) . https://dx.doi.org/10.2174/1381612811319140012
DOI https://dx.doi.org/10.2174/1381612811319140012 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Microvascular Function/Dysfunction Downstream a Coronary Stenosis
Current Pharmaceutical Design Mining for Protein Kinase Substrates: Integration of Biochemistry, Genetics and Proteomics
Current Proteomics Current Nervous System Related Drug Targets for the Treatment of Amyotrophic Lateral Sclerosis
Current Pharmaceutical Design Lost in Translation: What is Limiting Cardiomyoplasty and Can Tissue Engineering Help?
Current Stem Cell Research & Therapy Exercise and Stevia Rebaudiana (R) Extracts Attenuate Diabetic Cardiomyopathy in Type 2 Diabetic Rats: Possible Underlying Mechanisms
Endocrine, Metabolic & Immune Disorders - Drug Targets Prevalence of Major Cardiac Events of Anthracycline-Induced Cardiotoxicity in Southwestern Iran: Different Response Patterns to Cumulative Dose
Current Drug Therapy PET Measurements of cAMP-Mediated Phosphodiesterase-4 with (R)-[11C]Rolipram
Current Radiopharmaceuticals Thrombotic Thrombocytopenic Purpura and Anti-Thrombotic Therapy Targeted to Von Willebrand Factor
Current Vascular Pharmacology Changes in Market Share of Biologic and Targeted Synthetic Disease-Modifying Anti-Rheumatic Drugs for Treatment of Rheumatoid Arthritis: Results from the Ontario Best-Practice Research Initiative Database
Current Rheumatology Reviews Antioxidant Mechanisms in Nonalcoholic Fatty Liver Disease
Current Drug Targets Clinical Application of Tissue Doppler Imaging in Coronary Artery Diseases and Heart Failure
Recent Patents on Medical Imaging Nanocarriers Assisted siRNA Gene Therapy for the Management of Cardiovascular Disorders
Current Pharmaceutical Design 10 Years of SELDI: What Have we Learnt?
Current Proteomics NGS Technologies as a Turning Point in Rare Disease Research , Diagnosis and Treatment
Current Medicinal Chemistry Sex-Gender Differences in Diabetes Vascular Complications and Treatment
Endocrine, Metabolic & Immune Disorders - Drug Targets PET Imaging and Coronary Circulatory Function: Non-Invasive Mechanistic Insights and Cardiovascular Prognosis
Current Cardiology Reviews Editorial (Thematic Issue: Mechanistic Biomarkers: The Field for the Development of Non-Pharmaceutical and Pharmaceutical Approaches to Diagnostics, Prevention and Treatment of Chronic Diseases)
Current Pharmaceutical Design Cardiac Complications Attributed to Hydroxychloroquine: A Systematic Review of the Literature Pre-COVID-19
Current Cardiology Reviews Characterization of Supraventricular Tachycardia in Infants: Clinical and Instrumental Diagnosis
Current Pharmaceutical Design Erythropoietin and Oxidative Stress
Current Neurovascular Research