Cardiolipin Remodeling in the Heart
Abstract
Cardiolipin (CL) is a mitochondrial phospholipid that fundamentally contributes to the function of many proteins in the inner mitochondrial membrane, where it is actively involved in the integrity and flux of the electron transport chain. In the heart, functional CL is linoleic acid rich, and the loss of linoleic acid content is associated with cardiac disorders including ischemia and reperfusion, heart failure, and diabetes, as well as the X-linked recessive disease, Barth syndrome. To attain its high levels of linoleic acid, newly synthesized CL must initially undergo remodeling. CL modification and depletion by pathological processes may represent a failure of this remodeling pathway or activation of an alternative "pathological remodeling" pathway that causes the substitution of higher molecular weight, polyunsaturated fatty acyl side chains such as arachidonic or docosahexaenoic acid onto CL. This remodeling may occur in response to the alteration of CL by oxidative mechanisms, but the substituted side chains can also provoke further oxidation of CL. It is increasingly thought that cardiac pathology may result, at least partially, due to changes in CL resulting from the pathological remodeling process. Dietary interventions may restore CL to its linoleic acid-rich form and improve cardiac function by redirecting the remodeling process.
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In the heart, cardiolipin has a high content of linoleic acid that is essential for its ability to promote ETC complex III and IV activity.
“In the heart, cardiolipin is noted to have a high content of linoleic acid that is essential for its ability to promote ETC complex III and IV activity (396).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [396]
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Redox regulation of mitochondrial function
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The complexity of cardiolipin in health and disease
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- Authors
- Sparagna, G. C., & Lesnefsky, E. J.
- Affiliations
- University of Colorado Boulder (US)
- Veterans Health Administration (US)
- Corresponding author
- Sparagna, Genevieve C
- Venue
- Journal of Cardiovascular Pharmacology
- Published
- 2009-04
- Volume
- 53
- Issue
- 4
- Pages
- 290-301
- ISSN
- 0160-2446 (ISSN-L)
- OpenAlex
- W1964257657
- Cited by
- 128
- References
- 161
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 1 · 2023: 5 · 2022: 4 · 2021: 8 · 2020: 5 · 2019: 7 · 2018: 6 · 2017: 6 · 2016: 9 · 2015: 11 · 2014: 11 · 2013: 12 · 2012: 17
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cardiovascular Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (2P01 AG 15885, P01AG015885)
- National Heart, Lung, and Blood Institute (R21HL084129)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- cardiolipin remodeling, linoleic acid, mitochondrial phospholipids, inner mitochondrial membrane, electron transport chain, myocardial ischemia-reperfusion injury, heart failure, diabetes mellitus, Barth syndrome, cardiolipin oxidation, dietary intervention, cardiac function
- MeSH terms
- Animals, Cardiolipins, Electron Transport Complex IV, Humans, Ischemia, Mitochondria, Heart, Myocardium, Electron Transport Complex III, Molecular Structure, Apoptosis
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