Abstract
The natural polyamines spermine, spermidine and putrescine, polycationic molecules at physiological pH, interact with mitochondrial membranes at two specific binding sites exhibiting low affinity and high binding capacity. This binding represents the first step in the electrophoretic mechanism of polyamine transport into mitochondria. Spermine accumulated into the mitochondrial matrix is able to flow out by an electroneutral mechanism. This process promotes bi-directional transport of polyamines in and out of mitochondria, driven by electrical potential and pH gradient, respectively. Polyamines and biogenic amines are oxidized by cytosolic and mitochondrial amine oxidases with the production of hydrogen peroxide and aldehydes, both of which are involved in the induction and / or amplification of the mitochondrial permeability transition (MPT). This phenomenon, which provokes a bioenergetic collapse and redox catastrophe, is strongly inhibited by polyamines in isolated mitochondria. Monoamines also exhibit an inhibitory effect at higher concentrations, but at low concentrations behave as inducer agents. MPT is characterized by the opening of a channel, the transition pore, which permits nonspecific bi-directional traffic of solutes across the inner membrane, leading to swelling of the organelle and release of cytochrome c and apoptosis-inducing factors. These proteins in turn activate the caspase-cascade, which triggers the apoptotic pathway. Depending on their cytosolic concentration, metabolic conditions and cell type, polyamines act as promoting, modulating or protective agents in mitochondrial-mediated apoptosis. While their protective effect could reflect inhibition of MPT and retention of cytochrome c, the promoting effect can be explained by the generation of reactive oxygen species that induce the opposite effect on MPT and cytochrome c release. Polyamines and other active amines can also participate in the regulation of apoptotic pathways by interacting with the mitochondrial tyrosine phosphorylation / dephosphorylation system. Future studies of the multifaceted interactions of polyamines with mitochondria will thus have a substantial impact on our understanding of the physiology of cell proliferation death at several mechanistic levels.
Keywords: polyamines, biogenic amines, mitochondria, permeability transition, apoptosis
Current Medicinal Chemistry
Title: Interaction of Biologically Active Amines with Mitochondria and Their Role in the Mitochondrial-Mediated Pathway of Apoptosis
Volume: 11 Issue: 17
Author(s): A. Toninello, M. Salvi and B. Mondovì
Affiliation:
Keywords: polyamines, biogenic amines, mitochondria, permeability transition, apoptosis
Abstract: The natural polyamines spermine, spermidine and putrescine, polycationic molecules at physiological pH, interact with mitochondrial membranes at two specific binding sites exhibiting low affinity and high binding capacity. This binding represents the first step in the electrophoretic mechanism of polyamine transport into mitochondria. Spermine accumulated into the mitochondrial matrix is able to flow out by an electroneutral mechanism. This process promotes bi-directional transport of polyamines in and out of mitochondria, driven by electrical potential and pH gradient, respectively. Polyamines and biogenic amines are oxidized by cytosolic and mitochondrial amine oxidases with the production of hydrogen peroxide and aldehydes, both of which are involved in the induction and / or amplification of the mitochondrial permeability transition (MPT). This phenomenon, which provokes a bioenergetic collapse and redox catastrophe, is strongly inhibited by polyamines in isolated mitochondria. Monoamines also exhibit an inhibitory effect at higher concentrations, but at low concentrations behave as inducer agents. MPT is characterized by the opening of a channel, the transition pore, which permits nonspecific bi-directional traffic of solutes across the inner membrane, leading to swelling of the organelle and release of cytochrome c and apoptosis-inducing factors. These proteins in turn activate the caspase-cascade, which triggers the apoptotic pathway. Depending on their cytosolic concentration, metabolic conditions and cell type, polyamines act as promoting, modulating or protective agents in mitochondrial-mediated apoptosis. While their protective effect could reflect inhibition of MPT and retention of cytochrome c, the promoting effect can be explained by the generation of reactive oxygen species that induce the opposite effect on MPT and cytochrome c release. Polyamines and other active amines can also participate in the regulation of apoptotic pathways by interacting with the mitochondrial tyrosine phosphorylation / dephosphorylation system. Future studies of the multifaceted interactions of polyamines with mitochondria will thus have a substantial impact on our understanding of the physiology of cell proliferation death at several mechanistic levels.
Export Options
About this article
Cite this article as:
Toninello A., Salvi M. and Mondovì B., Interaction of Biologically Active Amines with Mitochondria and Their Role in the Mitochondrial-Mediated Pathway of Apoptosis, Current Medicinal Chemistry 2004; 11 (17) . https://dx.doi.org/10.2174/0929867043364559
DOI https://dx.doi.org/10.2174/0929867043364559 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
![](/images/wayfinder.jpg)
- 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
-
Treatment and Outcome of Pulmonary Arterial Hypertension in HIVInfected Patients: A Review of the Literature
Current HIV Research The Role of Transcription Factors in the Formation of an Arrhythmogenic Substrate in Congestive Human Heart Failure
Current Medicinal Chemistry Antihistamines: Past Answers and Present Questions
Current Drug Safety Therapeutic Peptides: New Arsenal Against Drug Resistant Pathogens
Current Pharmaceutical Design The Transcriptional Regulation of the Human CYP2C Genes
Current Drug Metabolism The Emerging Role of MicroRNA in Schizophrenia
CNS & Neurological Disorders - Drug Targets Inflammation-Mediating Proteases: Structure, Function in (Patho) Physiology and Inhibition
Protein & Peptide Letters Inhibition of Renin-Angiotensin System and Advanced Glycation End Products Formation: A Promising Therapeutic Approach Targeting on Cardiovascular Diseases
Cardiovascular & Hematological Agents in Medicinal Chemistry Current and Potential Anticancer Drugs Targeting Members of the UHRF1 Complex Including Epigenetic Modifiers
Recent Patents on Anti-Cancer Drug Discovery Familial Hypercholesterolemia: Etiology, Diagnosis and New Treatment Options
Current Pharmaceutical Design A Patient with COVID-19 Pneumonia Presenting with Plural Effusion: A Case Report
Infectious Disorders - Drug Targets Effects of Vitamin D Levels on Cardiovascular Diseases: A Systematic Review
Current Nutrition & Food Science Microdialysis in Drug Discovery
Current Drug Discovery Technologies Targeting Bacterial Metalloenzymes: A New Strategy for the Development of Anti-Infective Agents
Anti-Infective Agents in Medicinal Chemistry Regulatory Roles of the Ubiquitin-Proteasome System in Cardiomyocyte Apoptosis
Current Molecular Medicine A Comprehensive Systemic Literature Review of Pericardial Decompression Syndrome: Often Unrecognized and Potentially Fatal Syndrome
Current Cardiology Reviews Glycosaminoglycans, Protein Aggregation and Neurodegeneration
Current Protein & Peptide Science Apelin Receptor Dimerization and Oligomerization
Current Molecular Pharmacology Endothelin Receptor Antagonists: An Overview of Their Synthesis and Structure-Activity Relationship
Mini-Reviews in Medicinal Chemistry Twin-to-Twin Transfusion Syndrome: From Placental Anastomoses to Long-Term Neurodevelopmental Outcome
Current Pediatric Reviews