Role of cardiolipin peroxidation and Ca2+ in mitochondrial dysfunction and disease

Abstract Cardiolipin is a unique phospholipid which is almost exclusively located at the level of the inner mitochondrial membrane where it is biosynthesized. This phospholipid is known to be intimately involved in several mitochondrial bioenergetic processes. In addition, cardiolipin also has activ...

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Bibliographic Details
Published in:Cell calcium (Edinburgh) 2009-06, Vol.45 (6), p.643-650
Main Authors: Paradies, Giuseppe, Petrosillo, Giuseppe, Paradies, Valeria, Ruggiero, Francesca M
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
Ca2
Calcium - metabolism
Cardiolipin
Cardiolipins - metabolism
Cardiolipins - physiology
Cytochromes c - metabolism
Ischemia - metabolism
Lipid Peroxidation - drug effects
Mitochondria - drug effects
Mitochondria - physiology
Mitochondrial dysfunction
Mitochondrial Membrane Transport Proteins - physiology
Physiopathology
Reactive Oxygen Species - metabolism
ROS
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Summary:Abstract Cardiolipin is a unique phospholipid which is almost exclusively located at the level of the inner mitochondrial membrane where it is biosynthesized. This phospholipid is known to be intimately involved in several mitochondrial bioenergetic processes. In addition, cardiolipin also has active roles in several of the mitochondrial-dependent steps of apoptosis and in mitochondrial membrane dynamics. Alterations in cardiolipin structure, content and acyl chains composition have been associated with mitochondrial dysfunction in multiple tissues in several physiopathological conditions, including ischemia/reperfusion, different thyroid states, diabetes, aging and heart failure. Cardiolipin is particularly susceptible to ROS attack due to its high content of unsaturated fatty acids. Oxidative damage to cardiolipin would negatively impact the biochemical function of the mitochondrial membranes altering membrane fluidity, ion permeability, structure and function of components of the mitochondrial electron transport chain, resulting in reduced mitochondrial oxidative phosphorylation efficiency and apoptosis. Diseases in which mitochondrial dysfunction has been linked to cardiolipin peroxidation are described. Ca2+ , particularly at high concentrations, appears to have several negative effects on mitochondrial function, some of these effects being linked to CL peroxidation. Cardiolipin peroxidation has been shown to participate, together with Ca2+ , in mitochondrial permeability transition. In this review, we provide an overview of the role of CL peroxidation and Ca2+ in mitochondrial dysfunction and disease.
ISSN:0143-4160
1532-1991
DOI:10.1016/j.ceca.2009.03.012