The Role of Cardiolipin in Mitochondrial Function and Neurodegenerative Diseases

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2024 Apr 12

PMID 38607048

Authors

Jose M Fuentes

Patricia Morcillo

Affiliations

Soon will be listed here.

Abstract

Cardiolipin (CL) is a mitochondria-exclusive phospholipid synthesized in the inner mitochondrial membrane. CL plays a key role in mitochondrial membranes, impacting a plethora of functions this organelle performs. Consequently, it is conceivable that abnormalities in the CL content, composition, and level of oxidation may negatively impact mitochondrial function and dynamics, with important implications in a variety of diseases. This review concentrates on papers published in recent years, combined with basic and underexplored research in CL. We capture new findings on its biological functions in the mitochondria, as well as its association with neurodegenerative diseases such as Alzheimer's disease or Parkinson's disease. Lastly, we explore the potential applications of CL as a biomarker and pharmacological target to mitigate mitochondrial dysfunction.

Citing Articles

Molecular Symphony of Mitophagy: Ubiquitin-Specific Protease-30 as a Maestro for Precision Management of Neurodegenerative Diseases.

Siwach A, Patel H, Khairnar A, Parekh P CNS Neurosci Ther. 2025; 31(1):e70192.

PMID: 39840724 PMC: 11751875. DOI: 10.1111/cns.70192.

Phospholipid biosynthesis regulation for improving pigment production by in response to ammonium chloride stress.

Jiang X, Hong X, Wang Z, Liu J, Zhong H, Ren J Appl Environ Microbiol. 2024; 90(10):e0114624.

PMID: 39287399 PMC: 11497785. DOI: 10.1128/aem.01146-24.

References

Rampelt H, Wollweber F, Gerke C, de Boer R, van der Klei I, Bohnert M . Assembly of the Mitochondrial Cristae Organizer Mic10 Is Regulated by Mic26-Mic27 Antagonism and Cardiolipin. J Mol Biol. 2018; 430(13):1883-1890. DOI: 10.1016/j.jmb.2018.04.037. View

Seyfried T, Choi H, Chevalier A, Hogan D, Akgoc Z, Schneider J . Sex-Related Abnormalities in Substantia Nigra Lipids in Parkinson's Disease. ASN Neuro. 2018; 10:1759091418781889. PMC: 6024349. DOI: 10.1177/1759091418781889. View

Schlame M, Brody S, Hostetler K . Mitochondrial cardiolipin in diverse eukaryotes. Comparison of biosynthetic reactions and molecular acyl species. Eur J Biochem. 1993; 212(3):727-35. DOI: 10.1111/j.1432-1033.1993.tb17711.x. View

Ge Y, Boopathy S, Nguyen T, Lugo C, Chao L . Absence of Cardiolipin From the Outer Leaflet of a Mitochondrial Inner Membrane Mimic Restricts Opa1-Mediated Fusion. Front Mol Biosci. 2022; 8:769135. PMC: 8728091. DOI: 10.3389/fmolb.2021.769135. View

Dudek J, Cheng I, Balleininger M, Vaz F, Streckfuss-Bomeke K, Hubscher D . Cardiolipin deficiency affects respiratory chain function and organization in an induced pluripotent stem cell model of Barth syndrome. Stem Cell Res. 2013; 11(2):806-19. DOI: 10.1016/j.scr.2013.05.005. View

Huang Y, Powers C, Madala S, Greis K, Haffey W, Towbin J . Cardiac metabolic pathways affected in the mouse model of barth syndrome. PLoS One. 2015; 10(6):e0128561. PMC: 4451073. DOI: 10.1371/journal.pone.0128561. View

Li Y, Lou W, Raja V, Denis S, Yu W, Schmidtke M . Cardiolipin-induced activation of pyruvate dehydrogenase links mitochondrial lipid biosynthesis to TCA cycle function. J Biol Chem. 2019; 294(30):11568-11578. PMC: 6663869. DOI: 10.1074/jbc.RA119.009037. View

Koob S, Barrera M, Anand R, Reichert A . The non-glycosylated isoform of MIC26 is a constituent of the mammalian MICOS complex and promotes formation of crista junctions. Biochim Biophys Acta. 2015; 1853(7):1551-63. DOI: 10.1016/j.bbamcr.2015.03.004. View

Monteiro-Cardoso V, Oliveira M, Melo T, Domingues M, Moreira P, Ferreiro E . Cardiolipin profile changes are associated to the early synaptic mitochondrial dysfunction in Alzheimer's disease. J Alzheimers Dis. 2014; 43(4):1375-92. DOI: 10.3233/JAD-141002. View

10.

Kirkinezos I, Bacman S, Hernandez D, Oca-Cossio J, Arias L, Perez-Pinzon M . Cytochrome c association with the inner mitochondrial membrane is impaired in the CNS of G93A-SOD1 mice. J Neurosci. 2005; 25(1):164-72. PMC: 6725219. DOI: 10.1523/JNEUROSCI.3829-04.2005. View

11.

Kagan V, Tyurin V, Jiang J, Tyurina Y, Ritov V, Amoscato A . Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors. Nat Chem Biol. 2006; 1(4):223-32. DOI: 10.1038/nchembio727. View

12.

Karaa A, Bertini E, Carelli V, Cohen B, Enns G, Falk M . Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial. Neurology. 2023; 101(3):e238-e252. PMC: 10382259. DOI: 10.1212/WNL.0000000000207402. View

13.

Baker C, Ball W, Pryce E, Gohil V . Specific requirements of nonbilayer phospholipids in mitochondrial respiratory chain function and formation. Mol Biol Cell. 2016; 27(14):2161-71. PMC: 4945136. DOI: 10.1091/mbc.E15-12-0865. View

14.

Zarrouk A, Debbabi M, Bezine M, Karym E, Badreddine A, Rouaud O . Lipid Biomarkers in Alzheimer's Disease. Curr Alzheimer Res. 2017; 15(4):303-312. DOI: 10.2174/1567205014666170505101426. View

15.

Oemer G, Koch J, Wohlfarter Y, Alam M, Lackner K, Sailer S . Phospholipid Acyl Chain Diversity Controls the Tissue-Specific Assembly of Mitochondrial Cardiolipins. Cell Rep. 2020; 30(12):4281-4291.e4. DOI: 10.1016/j.celrep.2020.02.115. View

16.

Aufschnaiter A, Kohler V, Diessl J, Peselj C, Carmona-Gutierrez D, Keller W . Mitochondrial lipids in neurodegeneration. Cell Tissue Res. 2016; 367(1):125-140. PMC: 5203858. DOI: 10.1007/s00441-016-2463-1. View

17.

Gautam M, Genc B, Helmold B, Ahrens A, Kuka J, Makrecka-Kuka M . SBT-272 improves TDP-43 pathology in ALS upper motor neurons by modulating mitochondrial integrity, motility, and function. Neurobiol Dis. 2023; 178:106022. DOI: 10.1016/j.nbd.2023.106022. View

18.

Lee R, Gao J, Siira S, Shearwood A, Ermer J, Hofferek V . Cardiolipin is required for membrane docking of mitochondrial ribosomes and protein synthesis. J Cell Sci. 2020; 133(14). DOI: 10.1242/jcs.240374. View

19.

Friedman J, Mourier A, Yamada J, McCaffery J, Nunnari J . MICOS coordinates with respiratory complexes and lipids to establish mitochondrial inner membrane architecture. Elife. 2015; 4. PMC: 4434539. DOI: 10.7554/eLife.07739. View

20.

Anzmann A, Sniezek O, Pado A, Busa V, Vaz F, Kreimer S . Diverse mitochondrial abnormalities in a new cellular model of TAFFAZZIN deficiency are remediated by cardiolipin-interacting small molecules. J Biol Chem. 2021; 297(3):101005. PMC: 8384898. DOI: 10.1016/j.jbc.2021.101005. View