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The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.

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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Research works printed but not linked: 24

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Metadata

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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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