Role of cardiolipin alterations in mitochondrial dysfunction and disease

• Published in: American Journal of Physiology: Cell Physiology 2007-01, Vol.292 (1), p.C33-C44
• Main Authors: Chicco, Adam J, Sparagna, Genevieve C
• Format: Article
• Language: English
• Subjects: Aging; Aging - metabolism; Animals; Cardiac Output, Low - metabolism; Cardiac Output, Low - physiopathology; Cardiolipins - biosynthesis; Cardiolipins - metabolism; Cardiomyopathy, Dilated - genetics; Cardiomyopathy, Dilated - metabolism; Cardiomyopathy, Dilated - physiopathology; Cells; Disease; Genetic Diseases, X-Linked - metabolism; Genetic Diseases, X-Linked - physiopathology; Heart failure; Humans; Hypothyroidism - metabolism; Hypothyroidism - physiopathology; Ischemia - metabolism; Ischemia - physiopathology; Lipids; Metabolism; Mitochondria - metabolism; Syndrome
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00243.2006

Department of Integrative Physiology, University of Colorado at Boulder, Boulder, Colorado Submitted 4 May 2006 ; accepted in final form 1 August 2006 Cardiolipin (CL) is a structurally unique dimeric phospholipid localized in the inner mitochondrial membrane where it is required for optimal mitochondrial function. In addition to its role in maintaining membrane potential and architecture, CL is known to provide essential structural and functional support to several proteins involved in mitochondrial bioenergetics. A loss of CL content, alterations in its acyl chain composition, and/or CL peroxidation have been associated with mitochondrial dysfunction in multiple tissues in a variety of pathological conditions, including ischemia, hypothyroidism, aging, and heart failure. Recently, aberrations in CL metabolism have been implicated as a primary causative factor in the cardioskeletal myopathy known as Barth syndrome, underscoring an important role of CL in human health and disease. The purpose of this review is to provide an overview of evidence that has linked changes in the CL profile to mitochondrial dysfunction in various pathological conditions. In addition, a brief overview of CL function and biosynthesis, and a discussion of methods used to examine CL in biological tissues are provided. phospholipid; metabolism; heart failure; aging; hypothyroidism; lipid peroxidation; oxidative stress; diet; ischemia Address for reprint requests and other correspondence: G. C. Sparagna, Dept. of Integrative Physiology, Univ. of Colorado at Boulder, Campus Box 354, Boulder, CO 80309-0354 (e-mail: sparagna{at}spot.colorado.edu )