Concentration-dependent effects of nitric oxide on mitochondrial permeability transition and cytochrome c release - PubMed (original) (raw)

. 2000 Jul 7;275(27):20474-9.

doi: 10.1074/jbc.M001077200.

Affiliations

• PMID: 10791954
• DOI: 10.1074/jbc.M001077200

Free article

Concentration-dependent effects of nitric oxide on mitochondrial permeability transition and cytochrome c release

P S Brookes et al. J Biol Chem. 2000.

Free article

Abstract

The mitochondrial permeability transition pore (PTP) and associated release of cytochrome c are thought to be important in the apoptotic process. Nitric oxide (NO( small middle dot)) has been reported to inhibit apoptosis by acting on a variety of extra-mitochondrial targets. The relationship between cytochrome c release and PTP opening, and the effects of NO( small middle dot) are not clearly established. Nitric oxide, S-nitrosothiols and peroxynitrite are reported to variously inhibit or promote PTP opening. In this study the effects of NO( small middle dot) on the PTP were characterized by exposing isolated rat liver mitochondria to physiological and pathological rates of NO( small middle dot) released from NONOate NO( small middle dot) donors. Nitric oxide reversibly inhibited PTP opening with an IC(50) of 11 nm NO( small middle dot)/s, which can be readily achieved in vivo by NO( small middle dot) synthases. The mechanism involved mitochondrial membrane depolarization and inhibition of Ca(2+) accumulation. At supraphysiological release rates (>2 micrometer/s) NO( small middle dot) accelerated PTP opening. Substantial cytochrome c release occurred with only a 20% change in mitochondrial swelling, was an early event in the PTP, and was also inhibited by NO( small middle dot). Furthermore, NO( small middle dot) exposure resulted in significantly lower cytochrome c release for the same degree of PTP opening. It is proposed that this pathway represents an additional mechanism underlying the antiapoptotic effects of NO( small middle dot).

PubMed Disclaimer

Similar articles

• Nitric oxide and differential effects of ATP on mitochondrial permeability transition.
  Piantadosi CA, Tatro LG, Whorton AR. Piantadosi CA, et al. Nitric Oxide. 2002 Feb;6(1):45-60. doi: 10.1006/niox.2001.0368. Nitric Oxide. 2002. PMID: 11829534
• Bcl-2 does not inhibit the permeability transition pore in mouse liver mitochondria.
  Yang JC, Kahn A, Cortopassi G. Yang JC, et al. Toxicology. 2000 Oct 26;151(1-3):65-72. doi: 10.1016/s0300-483x(00)00298-5. Toxicology. 2000. PMID: 11074301
• Nitric oxide donors, nitrosothiols and mitochondrial respiration inhibitors induce caspase activation by different mechanisms.
  Borutaite V, Morkuniene R, Brown GC. Borutaite V, et al. FEBS Lett. 2000 Feb 11;467(2-3):155-9. doi: 10.1016/s0014-5793(00)01140-6. FEBS Lett. 2000. PMID: 10675529
• [The research method for investigating the role of the mitochondrial permeability transition pore in cell death].
  Ishida H. Ishida H. Nihon Yakurigaku Zasshi. 2004 May;123(5):329-34. doi: 10.1254/fpj.123.329. Nihon Yakurigaku Zasshi. 2004. PMID: 15118257 Review. Japanese.
• Nitric oxide, cytochrome c and mitochondria.
  Brown GC, Borutaite V. Brown GC, et al. Biochem Soc Symp. 1999;66:17-25. doi: 10.1042/bss0660017. Biochem Soc Symp. 1999. PMID: 10989653 Review.

Cited by

• Magnetic Stimulation as a Therapeutic Approach for Brain Modulation and Repair: Underlying Molecular and Cellular Mechanisms.
  Dufor T, Lohof AM, Sherrard RM. Dufor T, et al. Int J Mol Sci. 2023 Nov 17;24(22):16456. doi: 10.3390/ijms242216456. Int J Mol Sci. 2023. PMID: 38003643 Free PMC article. Review.
• Role of angiotensin II in aging.
  Yi W, Chen F, Zhang H, Tang P, Yuan M, Wen J, Wang S, Cai Z. Yi W, et al. Front Aging Neurosci. 2022 Dec 2;14:1002138. doi: 10.3389/fnagi.2022.1002138. eCollection 2022. Front Aging Neurosci. 2022. PMID: 36533172 Free PMC article. Review.
• Nitric oxide regulation of cellular metabolism: Adaptive tuning of cellular energy.
  Pappas G, Wilkinson ML, Gow AJ. Pappas G, et al. Nitric Oxide. 2023 Feb 1;131:8-17. doi: 10.1016/j.niox.2022.11.006. Epub 2022 Dec 5. Nitric Oxide. 2023. PMID: 36470373 Free PMC article. Review.
• Analysis of Mitochondrial Function, Structure, and Intracellular Organization In Situ in Cardiomyocytes and Skeletal Muscles.
  Kuznetsov AV, Javadov S, Margreiter R, Hagenbuchner J, Ausserlechner MJ. Kuznetsov AV, et al. Int J Mol Sci. 2022 Feb 18;23(4):2252. doi: 10.3390/ijms23042252. Int J Mol Sci. 2022. PMID: 35216368 Free PMC article. Review.
• Mitostasis, Calcium and Free Radicals in Health, Aging and Neurodegeneration.
  Godoy JA, Rios JA, Picón-Pagès P, Herrera-Fernández V, Swaby B, Crepin G, Vicente R, Fernández-Fernández JM, Muñoz FJ. Godoy JA, et al. Biomolecules. 2021 Jul 10;11(7):1012. doi: 10.3390/biom11071012. Biomolecules. 2021. PMID: 34356637 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations

• Miscellaneous

  • NCI CPTAC Assay Portal