Induction of mitochondrial destabilization and necrotic cell death by apolar mitochondria-directed SOD mimetics

A. Szabó, Maria Balog, L. Márk, Gergely Montsko, Zsuzsanna Turi, F. Gallyas, B. Sümegi, T. Kalai, K. Hideg, Krisztina Kovacs

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

In this paper, we present evidence, for the first time, that increasing the lipophilicity of mitochondria targeting SOD mimetics reverses their cytoprotective properties, destabilizing the mitochondrial membrane system and promoting cell death. A new mitochondria-directed apolar SOD mimetic, HO-3814, was found to provoke mitochondrial swelling and loss of mitochondrial membrane potential, and these effects were not inhibited by cyclosporine A. HO-3814-induced cell death was predominantly necrotic, caspase-independent, and not affected by mitochondrial permeability transition inhibitors or cyclophilin D-suppression, inhibitors of mitogen-activated protein kinases or Akt, or various antioxidants. In contrast, Bcl-2 overexpression diminished the effects of HO-3814.

Original languageEnglish
Pages (from-to)476-487
Number of pages12
JournalMitochondrion
Volume11
Issue number3
DOIs
Publication statusPublished - May 2011

Fingerprint

Mitochondria
Cell Death
Mitochondrial Swelling
Mitochondrial Membrane Potential
Mitochondrial Membranes
Caspases
Mitogen-Activated Protein Kinases
Cyclosporine
Permeability
Antioxidants
cyclophilin D

Keywords

  • Mitochondria
  • Necrosis
  • SOD mimetic
  • Triphenylphosphonium
  • Tumor cell line

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Molecular Medicine

Cite this

Induction of mitochondrial destabilization and necrotic cell death by apolar mitochondria-directed SOD mimetics. / Szabó, A.; Balog, Maria; Márk, L.; Montsko, Gergely; Turi, Zsuzsanna; Gallyas, F.; Sümegi, B.; Kalai, T.; Hideg, K.; Kovacs, Krisztina.

In: Mitochondrion, Vol. 11, No. 3, 05.2011, p. 476-487.

Research output: Contribution to journalArticle

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AU - Balog, Maria

AU - Márk, L.

AU - Montsko, Gergely

AU - Turi, Zsuzsanna

AU - Gallyas, F.

AU - Sümegi, B.

AU - Kalai, T.

AU - Hideg, K.

AU - Kovacs, Krisztina

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AB - In this paper, we present evidence, for the first time, that increasing the lipophilicity of mitochondria targeting SOD mimetics reverses their cytoprotective properties, destabilizing the mitochondrial membrane system and promoting cell death. A new mitochondria-directed apolar SOD mimetic, HO-3814, was found to provoke mitochondrial swelling and loss of mitochondrial membrane potential, and these effects were not inhibited by cyclosporine A. HO-3814-induced cell death was predominantly necrotic, caspase-independent, and not affected by mitochondrial permeability transition inhibitors or cyclophilin D-suppression, inhibitors of mitogen-activated protein kinases or Akt, or various antioxidants. In contrast, Bcl-2 overexpression diminished the effects of HO-3814.

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