Mitochondrial Permeability Transition and Swelling Can Occur Reversibly without Inducing Cell Death in Intact Human Cells

doi:10.1006/excr.1998.4290

Experimental Cell Research

Volume 246, Issue 1, 10 January 1999, Pages 26-37

https://doi.org/10.1006/excr.1998.4290 Get rights and content

Abstract

Severe disruption of mitochondrial function is generally considered to provide a powerful trigger for apoptosis in mammalian cells. We report here that intact cells may undergo the mitochondrial permeability transition and mitochondria swell in a fully reversible manner, without inducing cell death. Cultured human osteosarcoma cells (143B TK⁻) stained with JC-1, MitoTracker dyes, or calcein plus Co²⁺were imaged by confocal microscopy to visualize changes of mitochondrial membrane potential (ΔΨ_m), morphology, and permeability transition, respectively, during treatment with a protonophore, carbonyl cyanidem-chlorophenylhydrazone (CCCP). Cells rapidly exhibited mitochondrial permeability transition and swelling after addition of CCCP, but the swelling subsided within hours, leaving mitochondria that appeared in punctate form, not filamentous as before CCCP treatment. Cyclosporin A impeded the permeability transition and swelling, although complete inhibition was not observed. Cells survived the dissipation of ΔΨ_mby CCCP for up to 6 h without developing any obvious cell damage or signs of apoptosis. With the restoration of ΔΨ_mafter removal of CCCP (following 6 h of CCCP treatment), permeability transition pores were closed. These results suggest that none of the following events represent a point of no return in the process of apoptotic cell death: loss of ΔΨ_m, mitochondrial permeability transition, or mitochondrial swelling.

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Citation Excerpt :
Mitochondria have an outer mitochondrial membrane (OMM) and an inner mitochondrial membrane (IMM) (Minamikawa et al., 1999). OMM is permeable for solutes with ionic/molecular masses below 6 kD (O'Rourke et al., 1994), while the inner mitochondrial membrane (IMM) has a number of specific channels for solute transport (Khmelinskii and Makarov, 2020, 2021a) and nonspecific permeability transport pores (PTP) (Minamikawa et al., 1999), which open in certain conditions, helping to control solute balance (Susin et al., 1998). It was found that PTPs open up to about 1.5 ± 0.1 nm (Susin et al., 1998; Khmelinskii & Makarov, 2021b).
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Regular ArticleMitochondrial Permeability Transition and Swelling Can Occur Reversibly without Inducing Cell Death in Intact Human Cells

Abstract

FEBS Lett.

Biochim. Biophys. Acta

Cell

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

Methods Enzymol.

Neuron

Exp. Cell Res.

Exp. Cell Res.

Biochim. Biophys. Acta

FEBS Lett.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Biophys. J.

FEBS Lett.

Biochim. Biophys. Acta

Regular Article
Mitochondrial Permeability Transition and Swelling Can Occur Reversibly without Inducing Cell Death in Intact Human Cells