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Cited by 262Sphingolipid Metabolism and SignalingMitochondrial Function and PathologyAutophagy in Disease and Therapy

Ceramide Interaction with the Respiratory Chain of Heart Mitochondria

Di Paola, Marco, Cocco, Tiziana, Lorusso, Michele·2000·Biochemistry
DOI 10.1021/bi9924415
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Abstract

A study is presented on the interaction of ceramide with the respiratory chain of rat heart mitochondria, and a comparison is made between the effects elicited by short- and long-chain ceramides. N-Acetylsphingosine (C(2)-ceramide) and N-palmitoylsphingosine (C(16)-ceramide) inhibited to the same extent the pyruvate+malate-dependent oxygen consumption. Succinate-supported respiration was also inhibited by ceramides, but this activity was substantially restored upon the addition of cytochrome c, which, on the contrary, was ineffective toward the ceramide-inhibited NADH-linked substrate oxidation. Direct measurements showed that short- and long-chain ceramides caused a large release of cytochrome c from mitochondria. The ceramide-dependent inhibition of pyruvate+malate and succinate oxidation caused reactive oxygen species to be produced at the level of either complex I or complex III. The activity of the cytochrome c oxidase, measured as ascorbate/TMPD oxidase activity, was significantly stimulated and inhibited by C(2)- and C(16)-ceramide, respectively. Similar effects were observed on the activity of the individual respiratory complexes isolated from bovine heart. Short- and long-chain ceramides had definitely different effects on the mitochondrial membrane potential. C(2)-ceramide caused an almost complete collapse of the respiration-dependent membrane potential, whereas C(16)-ceramide had a negligible effect. Similar results were obtained when the potential was generated in liposome-reconstituted complex III respiring at the steady-state. Furthermore, C(2)-ceramide caused a drop of the membrane potential generated by ATP hydrolysis instead of respiration, whereas C(16)-ceramide did not. Finally, only short-chain ceramides inhibited markedly the reactive oxygen species generation associated with membrane potential-dependent reverse electron flow from succinate to complex I. The emerging indication is that the short-chain ceramide-dependent collapse of membrane potential is a consequence of their ability to perturb the membrane structure, leading to an unspecific increase of its permeability.

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  • The production of ceramide and certain DAG species may feedback to further suppress the activity of respiratory chain complexes, which, associated with reduced expression of succinate dehydrogenase (complex II) induced by chronic fuel excess, is likely to impair electron transfer within the respiratory chain.

    “The production of ceramide and certain DAG species may, in turn, feedback to further suppress the activity of respiratory chain complexes [40, 41], which, associated with the reduced expression of succinate dehydrogenase (complex II) that is induced in response to chronic fuel excess, is likely to impair electron transfer within the respiratory chain.”

    From Proinflammatory NFkB signalling promotes mitochondrial dysfunction in skeletal muscle in response to cellular fuel overloading (2019) · cites this paper as [40]

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Authors
Di Paola, M., Cocco, T., & Lorusso, M.
Affiliations
  • Department of Medical Biochemistry and Biology and Centre for the Study of Mitochondria and Energy Metabolism (CNR), University of Bari, 70124 Bari, Italy
  • University of Bari Aldo Moro (IT)
Corresponding author
Lorusso, Michele
ORCID
Venue
Biochemistry
Publisher
American Chemical Society (ACS)
Published
2000-05-12
Volume
39
Issue
22
Pages
6660-6668
ISSN
  • 0006-2960 (ISSN-L)
  • 1520-4995
DOI
10.1021/bi9924415
OpenAlex
W2044325325
Cited by
262
References
19
Citations by year
2026: 8 · 2025: 8 · 2024: 3 · 2023: 23 · 2022: 12 · 2021: 10 · 2020: 7 · 2019: 5 · 2018: 8 · 2017: 5 · 2016: 8 · 2015: 11 · 2014: 5 · 2013: 12 · 2012: 15
FWCI
4.34
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
ceramide, heart mitochondria, electron transport chain, short-chain ceramides, long-chain ceramides, N-acetylsphingosine, cytochrome c release, reactive oxygen species, complex I, cytochrome bc1 complex, cytochrome c oxidase, mitochondrial membrane potential, membrane permeability, reverse electron flow, oxygen consumption inhibition
MeSH terms
Adenosine Triphosphate, Animals, Cattle, Ceramides, Cytochrome c Group, Electron Transport Complex IV, Electron Transport, Hydrogen Peroxide, Liposomes, Male, Membrane Potentials, Mitochondria, Heart, Multienzyme Complexes, NAD, Oxidation-Reduction, Oxygen Consumption, Rats, Wistar, Rats

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