The Structure of the Cardiac Mitochondria Respirasome Is Adapted for the β-Oxidation of Fatty Acids
- PMID: 38397087
- PMCID: PMC10889813
- DOI: 10.3390/ijms25042410
The Structure of the Cardiac Mitochondria Respirasome Is Adapted for the β-Oxidation of Fatty Acids
Abstract
It is well known that in the heart and kidney mitochondria, more than 95% of ATP production is supported by the β-oxidation of long-chain fatty acids. However, the β-oxidation of fatty acids by mitochondria has been studied much less than the substrates formed during the catabolism of carbohydrates and amino acids. In the last few decades, several discoveries have been made that are directly related to fatty acid oxidation. In this review, we made an attempt to re-evaluate the β-oxidation of long-chain fatty acids from the perspectives of new discoveries. The single set of electron transporters of the cardiac mitochondrial respiratory chain is organized into three supercomplexes. Two of them contain complex I, a dimer of complex III, and two dimers of complex IV. The third, smaller supercomplex contains a dimer of complex III and two dimers of complex IV. We also considered other important discoveries. First, the enzymes of the β-oxidation of fatty acids are physically associated with the respirasome. Second, the β-oxidation of fatty acids creates the highest level of QH2 and reverses the flow of electrons from QH2 through complex II, reducing fumarate to succinate. Third, β-oxidation is greatly stimulated in the presence of succinate. We argue that the respirasome is uniquely adapted for the β-oxidation of fatty acids. The acyl-CoA dehydrogenase complex reduces the membrane's pool of ubiquinone to QH2, which is instantly oxidized by the smaller supercomplex, generating a high energization of mitochondria and reversing the electron flow through complex II, which reverses the electron flow through complex I, increasing the NADH/NAD+ ratio in the matrix. The mitochondrial nicotinamide nucleotide transhydrogenase catalyzes a hydride (H-, a proton plus two electrons) transfer across the inner mitochondrial membrane, reducing the cytosolic pool of NADP(H), thus providing the heart with ATP for muscle contraction and energy and reducing equivalents for the housekeeping processes.
Keywords: heart mitochondria; oxidative phosphorylation; respirasome; respiratory chain; tricarboxylic acid cycle; ubiquinol; ubiquinone; β-oxidation of fatty acids.
Conflict of interest statement
The author declares no conflicts of interest.
Figures
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/10889813/bin/ijms-25-02410-g001.gif)
![Figure 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/10889813/bin/ijms-25-02410-g002.gif)
![Figure 3](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/10889813/bin/ijms-25-02410-g003.gif)
![Figure 4](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/10889813/bin/ijms-25-02410-g004.gif)
![Figure 5](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/10889813/bin/ijms-25-02410-g005.gif)
![Figure 6](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/10889813/bin/ijms-25-02410-g006.gif)
![Figure 7](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/10889813/bin/ijms-25-02410-g007.gif)
![Figure 8](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/10889813/bin/ijms-25-02410-g008.gif)
![Figure 9](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/10889813/bin/ijms-25-02410-g009.gif)
Similar articles
-
Mitochondrial fatty acid oxidation and the electron transport chain comprise a multifunctional mitochondrial protein complex.J Biol Chem. 2019 Aug 16;294(33):12380-12391. doi: 10.1074/jbc.RA119.008680. Epub 2019 Jun 24. J Biol Chem. 2019. PMID: 31235473 Free PMC article.
-
Long-Chain and Medium-Chain Fatty Acids in Energy Metabolism of Murine Kidney Mitochondria.Int J Mol Sci. 2022 Dec 26;24(1):379. doi: 10.3390/ijms24010379. Int J Mol Sci. 2022. PMID: 36613826 Free PMC article.
-
Kinetic evidence against partitioning of the ubiquinone pool and the catalytic relevance of respiratory-chain supercomplexes.Proc Natl Acad Sci U S A. 2014 Nov 4;111(44):15735-40. doi: 10.1073/pnas.1413855111. Epub 2014 Oct 20. Proc Natl Acad Sci U S A. 2014. PMID: 25331896 Free PMC article.
-
Complex II ambiguities-FADH2 in the electron transfer system.J Biol Chem. 2024 Jan;300(1):105470. doi: 10.1016/j.jbc.2023.105470. Epub 2023 Nov 22. J Biol Chem. 2024. PMID: 38118236 Free PMC article. Review.
-
Mitochondrial β-oxidation of saturated fatty acids in humans.Mitochondrion. 2019 May;46:73-90. doi: 10.1016/j.mito.2018.02.009. Epub 2018 Mar 15. Mitochondrion. 2019. PMID: 29551309 Review.
Cited by
-
Glycolipid Metabolic Disorders, Metainflammation, Oxidative Stress, and Cardiovascular Diseases: Unraveling Pathways.Biology (Basel). 2024 Jul 12;13(7):519. doi: 10.3390/biology13070519. Biology (Basel). 2024. PMID: 39056712 Free PMC article. Review.
References
-
- Spitzer J.J. CNS, and fatty acid metabolism. Physiologist. 1973;16:55–68. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources