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Role of Cardiolipin in Mitochondrial Function and Dynamics in Health and Disease: Molecular and Pharmacological Aspects
In eukaryotic cells, mitochondria are involved in a large array of metabolic and bioenergetic processes that are vital for cell survival. Phospholipids are the main building blocks of mitochondrial membranes. Cardiolipin (CL) is a unique phospholipid which is localized and synthesized in the inner m...
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Published in: | Cells (Basel, Switzerland) Switzerland), 2019-07, Vol.8 (7), p.728 |
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description | In eukaryotic cells, mitochondria are involved in a large array of metabolic and bioenergetic processes that are vital for cell survival. Phospholipids are the main building blocks of mitochondrial membranes. Cardiolipin (CL) is a unique phospholipid which is localized and synthesized in the inner mitochondrial membrane (IMM). It is now widely accepted that CL plays a central role in many reactions and processes involved in mitochondrial function and dynamics. Cardiolipin interacts with and is required for optimal activity of several IMM proteins, including the enzyme complexes of the electron transport chain (ETC) and ATP production and for their organization into supercomplexes. Moreover, CL plays an important role in mitochondrial membrane morphology, stability and dynamics, in mitochondrial biogenesis and protein import, in mitophagy, and in different mitochondrial steps of the apoptotic process. It is conceivable that abnormalities in CL content, composition and level of oxidation may negatively impact mitochondrial function and dynamics, with important implications in a variety of pathophysiological situations and diseases. In this review, we focus on the role played by CL in mitochondrial function and dynamics in health and diseases and on the potential of pharmacological modulation of CL through several agents in attenuating mitochondrial dysfunction. |
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Phospholipids are the main building blocks of mitochondrial membranes. Cardiolipin (CL) is a unique phospholipid which is localized and synthesized in the inner mitochondrial membrane (IMM). It is now widely accepted that CL plays a central role in many reactions and processes involved in mitochondrial function and dynamics. Cardiolipin interacts with and is required for optimal activity of several IMM proteins, including the enzyme complexes of the electron transport chain (ETC) and ATP production and for their organization into supercomplexes. Moreover, CL plays an important role in mitochondrial membrane morphology, stability and dynamics, in mitochondrial biogenesis and protein import, in mitophagy, and in different mitochondrial steps of the apoptotic process. It is conceivable that abnormalities in CL content, composition and level of oxidation may negatively impact mitochondrial function and dynamics, with important implications in a variety of pathophysiological situations and diseases. In this review, we focus on the role played by CL in mitochondrial function and dynamics in health and diseases and on the potential of pharmacological modulation of CL through several agents in attenuating mitochondrial dysfunction.</description><identifier>ISSN: 2073-4409</identifier><identifier>EISSN: 2073-4409</identifier><identifier>DOI: 10.3390/cells8070728</identifier><identifier>PMID: 31315173</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animals ; Antioxidants - pharmacology ; Apoptosis ; Barth Syndrome - metabolism ; Binding sites ; Bioenergetics ; Cardiolipin ; Cardiolipins - genetics ; Cardiolipins - metabolism ; Cell survival ; Crystal structure ; Diabetes Mellitus - metabolism ; Diphosphatidylglycerol ; Disease ; Electron transport chain ; Endoplasmic reticulum ; Energy ; Enzymes ; Fatty acids ; Glycerol ; Humans ; Kinases ; Membranes ; Metabolism ; Metabolites ; Mitochondria ; Mitochondria - drug effects ; Mitochondria - metabolism ; Mitochondrial Dynamics ; mitochondrial structure-function ; Morphology ; Mutation ; Myocardial Reperfusion Injury - metabolism ; Oxidation ; Oxidative Stress ; Parkinson Disease - metabolism ; Permeability ; pharmacological agents ; Phospholipids ; physiopathology ; Protein transport ; Proteins ; Review</subject><ispartof>Cells (Basel, Switzerland), 2019-07, Vol.8 (7), p.728</ispartof><rights>2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). 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Phospholipids are the main building blocks of mitochondrial membranes. Cardiolipin (CL) is a unique phospholipid which is localized and synthesized in the inner mitochondrial membrane (IMM). It is now widely accepted that CL plays a central role in many reactions and processes involved in mitochondrial function and dynamics. Cardiolipin interacts with and is required for optimal activity of several IMM proteins, including the enzyme complexes of the electron transport chain (ETC) and ATP production and for their organization into supercomplexes. Moreover, CL plays an important role in mitochondrial membrane morphology, stability and dynamics, in mitochondrial biogenesis and protein import, in mitophagy, and in different mitochondrial steps of the apoptotic process. It is conceivable that abnormalities in CL content, composition and level of oxidation may negatively impact mitochondrial function and dynamics, with important implications in a variety of pathophysiological situations and diseases. In this review, we focus on the role played by CL in mitochondrial function and dynamics in health and diseases and on the potential of pharmacological modulation of CL through several agents in attenuating mitochondrial dysfunction.</description><subject>Animals</subject><subject>Antioxidants - pharmacology</subject><subject>Apoptosis</subject><subject>Barth Syndrome - metabolism</subject><subject>Binding sites</subject><subject>Bioenergetics</subject><subject>Cardiolipin</subject><subject>Cardiolipins - genetics</subject><subject>Cardiolipins - metabolism</subject><subject>Cell survival</subject><subject>Crystal structure</subject><subject>Diabetes Mellitus - metabolism</subject><subject>Diphosphatidylglycerol</subject><subject>Disease</subject><subject>Electron transport chain</subject><subject>Endoplasmic reticulum</subject><subject>Energy</subject><subject>Enzymes</subject><subject>Fatty acids</subject><subject>Glycerol</subject><subject>Humans</subject><subject>Kinases</subject><subject>Membranes</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Mitochondria</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Mitochondrial Dynamics</subject><subject>mitochondrial structure-function</subject><subject>Morphology</subject><subject>Mutation</subject><subject>Myocardial Reperfusion Injury - metabolism</subject><subject>Oxidation</subject><subject>Oxidative Stress</subject><subject>Parkinson Disease - metabolism</subject><subject>Permeability</subject><subject>pharmacological agents</subject><subject>Phospholipids</subject><subject>physiopathology</subject><subject>Protein transport</subject><subject>Proteins</subject><subject>Review</subject><issn>2073-4409</issn><issn>2073-4409</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNpdks9rFDEUxwdRbKm9eZYBLx5cze9JPAhlbW2hRRE9hzcvmd0smcmazCj97zvbrWVrCCS8fPjwknyr6jUlHzg35CP6GIsmDWmYflYdM9LwhRDEPD_YH1WnpWzIPDRVlMiX1RGnnEra8OPq748UfZ26egnZhRTDNgz1PG_CmHCdBpcDxPpiGnAMaahhcPWX2wH6gGWHXXqI43pfDsVD8Z_qm9mIU4R8X_6-htwDpphWAWfVWdl6HMur6kUHsfjTh_Wk-nVx_nN5ubj-9vVqeXa9QCnEuOBCCGqkBMONo4YppbTshFGtd6TjqBtJhGHIwaNrfIfokKGX1HFUxCt-Ul3tvS7Bxm5z6CHf2gTB3hdSXlnIY8DoLZAGKbSuow6E4qJVXpGGau0QNGvb2fV579pObe8d-mHMEJ9In54MYW1X6Y9VqtGaslnw7kGQ0-_Jl9H2oey-EAafpmIZk8YQyckOffsfuklTHuanskwKzTmRlM7U-z2FOZWSfffYDCV2FxB7GJAZf3N4gUf4Xxz4He09uAA</recordid><startdate>20190716</startdate><enddate>20190716</enddate><creator>Paradies, Giuseppe</creator><creator>Paradies, Valeria</creator><creator>Ruggiero, Francesca M</creator><creator>Petrosillo, Giuseppe</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-8035-8368</orcidid></search><sort><creationdate>20190716</creationdate><title>Role of Cardiolipin in Mitochondrial Function and Dynamics in Health and Disease: Molecular and Pharmacological Aspects</title><author>Paradies, Giuseppe ; Paradies, Valeria ; Ruggiero, Francesca M ; Petrosillo, Giuseppe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c544t-34441955a939d19266685f496bed0f3c8750492c3aecd7efccdc2ce51d3c60e63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Antioxidants - pharmacology</topic><topic>Apoptosis</topic><topic>Barth Syndrome - metabolism</topic><topic>Binding sites</topic><topic>Bioenergetics</topic><topic>Cardiolipin</topic><topic>Cardiolipins - genetics</topic><topic>Cardiolipins - metabolism</topic><topic>Cell survival</topic><topic>Crystal structure</topic><topic>Diabetes Mellitus - metabolism</topic><topic>Diphosphatidylglycerol</topic><topic>Disease</topic><topic>Electron transport chain</topic><topic>Endoplasmic reticulum</topic><topic>Energy</topic><topic>Enzymes</topic><topic>Fatty acids</topic><topic>Glycerol</topic><topic>Humans</topic><topic>Kinases</topic><topic>Membranes</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Mitochondria</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>Mitochondrial Dynamics</topic><topic>mitochondrial structure-function</topic><topic>Morphology</topic><topic>Mutation</topic><topic>Myocardial Reperfusion Injury - metabolism</topic><topic>Oxidation</topic><topic>Oxidative Stress</topic><topic>Parkinson Disease - metabolism</topic><topic>Permeability</topic><topic>pharmacological agents</topic><topic>Phospholipids</topic><topic>physiopathology</topic><topic>Protein transport</topic><topic>Proteins</topic><topic>Review</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Paradies, Giuseppe</creatorcontrib><creatorcontrib>Paradies, Valeria</creatorcontrib><creatorcontrib>Ruggiero, Francesca M</creatorcontrib><creatorcontrib>Petrosillo, Giuseppe</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Biological Science Collection</collection><collection>ProQuest Biological Science Journals</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Cells (Basel, Switzerland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Paradies, Giuseppe</au><au>Paradies, Valeria</au><au>Ruggiero, Francesca M</au><au>Petrosillo, Giuseppe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of Cardiolipin in Mitochondrial Function and Dynamics in Health and Disease: Molecular and Pharmacological Aspects</atitle><jtitle>Cells (Basel, Switzerland)</jtitle><addtitle>Cells</addtitle><date>2019-07-16</date><risdate>2019</risdate><volume>8</volume><issue>7</issue><spage>728</spage><pages>728-</pages><issn>2073-4409</issn><eissn>2073-4409</eissn><abstract>In eukaryotic cells, mitochondria are involved in a large array of metabolic and bioenergetic processes that are vital for cell survival. Phospholipids are the main building blocks of mitochondrial membranes. Cardiolipin (CL) is a unique phospholipid which is localized and synthesized in the inner mitochondrial membrane (IMM). It is now widely accepted that CL plays a central role in many reactions and processes involved in mitochondrial function and dynamics. Cardiolipin interacts with and is required for optimal activity of several IMM proteins, including the enzyme complexes of the electron transport chain (ETC) and ATP production and for their organization into supercomplexes. Moreover, CL plays an important role in mitochondrial membrane morphology, stability and dynamics, in mitochondrial biogenesis and protein import, in mitophagy, and in different mitochondrial steps of the apoptotic process. It is conceivable that abnormalities in CL content, composition and level of oxidation may negatively impact mitochondrial function and dynamics, with important implications in a variety of pathophysiological situations and diseases. In this review, we focus on the role played by CL in mitochondrial function and dynamics in health and diseases and on the potential of pharmacological modulation of CL through several agents in attenuating mitochondrial dysfunction.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>31315173</pmid><doi>10.3390/cells8070728</doi><orcidid>https://orcid.org/0000-0001-8035-8368</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Animals Antioxidants - pharmacology Apoptosis Barth Syndrome - metabolism Binding sites Bioenergetics Cardiolipin Cardiolipins - genetics Cardiolipins - metabolism Cell survival Crystal structure Diabetes Mellitus - metabolism Diphosphatidylglycerol Disease Electron transport chain Endoplasmic reticulum Energy Enzymes Fatty acids Glycerol Humans Kinases Membranes Metabolism Metabolites Mitochondria Mitochondria - drug effects Mitochondria - metabolism Mitochondrial Dynamics mitochondrial structure-function Morphology Mutation Myocardial Reperfusion Injury - metabolism Oxidation Oxidative Stress Parkinson Disease - metabolism Permeability pharmacological agents Phospholipids physiopathology Protein transport Proteins Review |
title | Role of Cardiolipin in Mitochondrial Function and Dynamics in Health and Disease: Molecular and Pharmacological Aspects |
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