Effect of 6‐ketocholestanol on FCCP‐ and DNP‐induced uncoupling in plant mitochondria

Vianello, Angelo; Macrı̀, Francesco; Braidot, Enrico; Mokhova, E. N.

doi:10.1016/0014-5793(95)00431-8

Cited by 24 publications

(15 citation statements)

References 8 publications

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“…Starkov et al [4] found that kCh decreased the effect of uncouplers in heart mitochondria: kCh inhibited the collapse of membrane potential induced by CCP, FCCP and SF6847. Similarly, Vianello et al [5] described that kCh prevented or reversed the effect of uncouplers in plant mitochondria. However, in a recent work, Starkov et al [6] established that in in phospholipid planar membranes kCh stimulated, instead of inhibiting, the uncoupling effect of FCCP.…”

Section: Introductionmentioning

confidence: 81%

On the mechanism by which 6‐ketocholestanol protects mitochondria against uncoupling‐induced Ca²⁺ efflux

et al. 1996

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This work shows that 6-ketocholestanol (kCh) inhibits the effect of carbonyl cyanide-m-chlorophenyl hydrazone (CCP) on mitochondrial Ca 2÷ efflux. Such an effect proved to be caused by diminution of membrane fluidity, therefore, it is affected by the incubation temperature. Furthermore, kCh reversed CCPinduced Ca 2+ efflux depending on the accumulation of phosphate. It is also shown that kCh enhances the effect of carboxyatractyloside on membrane permeability transition.

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Section: Introductionmentioning

confidence: 81%

On the mechanism by which 6‐ketocholestanol protects mitochondria against uncoupling‐induced Ca²⁺ efflux

et al. 1996

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“…The excitation and emission wavelengths were 495 and 586 nm, respectively, with a 10-nm slit width for both emission and excitation (42). Unless otherwise K562 cells were loaded with JC-1 and then treated with 3 M Cs-5, BMAP-28, or 10 M FCCP as described above.…”

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confidence: 99%

BMAP-28, an Antibiotic Peptide of Innate Immunity, Induces Cell Death through Opening of the Mitochondrial Permeability Transition Pore

Risso¹,

Braidot

Sordano

et al. 2002

Molecular and Cellular Biology

140

111

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BMAP-28, a bovine antimicrobial peptide of the cathelicidin family, induces membrane permeabilization and death in human tumor cell lines and in activated, but not resting, human lymphocytes. In addition, we found that BMAP-28 causes depolarization of the inner mitochondrial membrane in single cells and in isolated mitochondria. The effect of the peptide was synergistic with that of Ca 2؉ and inhibited by cyclosporine, suggesting that depolarization depends on opening of the mitochondrial permeability transition pore. The occurrence of a permeability transition was investigated on the basis of mitochondrial permeabilization to calcein and cytochrome c release. We show that BMAP-28 permeabilizes mitochondria to entrapped calcein in a cyclosporine-sensitive manner and that it releases cytochrome c in situ. Our results demonstrate that BMAP-28 is an inducer of the mitochondrial permeability transition pore and that its cytotoxic potential depends on its effects on mitochondrial permeability.Mitochondria are the focus of intense research as major integrators and regulators of cell death pathways (7,8,10,15). Release of death-promoting factors by mitochondria has been reported as a regulatory event in apoptotic death mediated by different signals (20,35,37,39). Mitochondrial dysfunction may also cause necrotic death, and the role played by mitochondria has been well documented in several experimental systems (1,21,23,40). The central role of mitochondria as integrators of the death effector mechanisms is suggested by the fact that several signals derived either from external stimuli or from the cytosol or nucleus converge on mitochondria to trigger cell death (8).The human antimicrobial peptide hystatin 5 was recently added to the number of toxic agents that act through mitochondria. This molecule is cytotoxic to Candida albicans in a manner dependent on functionally active mitochondria, as inhibition of respiration protects the cells from its toxicity (16). Likewise, de-energized human cell lines are protected from the cytotoxic effects of other antimicrobial peptides such as the human defensins (25, 26) and the bovine BMAP-28, a cationic peptide of the cathelicidin family (34,36,45). The latter agent causes membrane permeabilization and death of activated human lymphocytes and tumor cells (34). The cytotoxic activity has been related to the structural features of the peptide, which consists of a cationic N-terminal sequence predicted to assume an amphipathic ␣-helical conformation (residues 1 to 18) and a C-terminal hydrophobic tail (residues 19 to 27). The C-terminal sequence seems to be crucial for the cytotoxic activity, as a great reduction of this effect is observed with the synthetic analogue BMAP-28(1-18) comprising the 18 N-terminal residues (36). A second requirement for cytotoxicity is an active metabolism of the target cells, as BMAP-28 is ineffective in nonrespiring cells (34).In view of these observations, we have investigated whether mitochondria are targets of the peptide itself and/or mediators of i...

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“…Jones (19) recently discussed the possible role of mitochondria and PTP as stress sensors and dispatchers of programmed cell death in animal and plant cells. Working with pea stem mitochondria, Vianello et al (20) showed that the lag phase preceding the ⌬⌿ collapse induced by carbonyl-cyanide-4-trifluoromethoxyphenylhydrazone (FCCP) or by carboxyatractylate was increased by CsA. However, their mitochondria did not exhibit high amplitude swelling, which was suggested to be an intrinsic characteristic of pea stem mitochondria (20).…”

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confidence: 99%

“…Working with pea stem mitochondria, Vianello et al (20) showed that the lag phase preceding the ⌬⌿ collapse induced by carbonyl-cyanide-4-trifluoromethoxyphenylhydrazone (FCCP) or by carboxyatractylate was increased by CsA. However, their mitochondria did not exhibit high amplitude swelling, which was suggested to be an intrinsic characteristic of pea stem mitochondria (20). This first attempt to substantiate the occurrence of MPT in plants remained thus inconclusive.…”

mentioning

confidence: 99%

Occurrence and Characteristics of the Mitochondrial Permeability Transition in Plants

Arpagaus

Rawyler

Braendle

2002

Journal of Biological Chemistry

132

103

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The behavior of purified potato mitochondria toward the main effectors of the animal mitochondrial permeability transition has been studied by light scattering, fluorescence, SDS-polyacrylamide gel electrophoresis, and immunoblotting techniques. The addition of Ca 2؉ induces a phosphate-dependent swelling that is fully inhibited by cyclosporin A if dithioerythritol is present. Mg 2؉ cannot be substituted for Ca 2؉ but competes with it. Disruption of the outer membrane and release of several proteins, including cytochrome c, occur upon completion of swelling. Ca 2؉ -induced swelling is delayed and its rate is decreased when pH is shifted from 7.4 to 6.6. It is accelerated by diamide, phenylarsine oxide, and linolenic acid. In the absence of Ca 2؉ , however, linolenic acid (<20 M) rapidly dissipates the succinate-driven membrane potential while having no effect on mitochondrial volume. Anoxic conditions favor in vitro swelling and the concomitant release of cytochrome c and of other proteins in a pH-dependent way. These data indicate that the classical mitochondrial permeability transition occurs also in plants. This may have important implications for our understanding of cell stress and death processes.Since the late 1970s, it has been known that animal mitochondria can experience a sudden increase in the permeability of their inner membrane to low and medium molecular weight compounds via the opening of a pore (1-3). This mitochondrial permeability transition pore (PTP) 1 is viewed as a multiprotein complex composed at least of the voltage-dependent anion channel, the adenine nucleotide translocator (AdNT), and cyclophilin-D, at the contact sites between outer and inner membranes (4). When the pore opens, solutes up to about 1.5 kDa can pass through the inner membrane, a process known as the mitochondrial permeability transition (MPT). Subsequently, the membrane potential (⌬⌿) decays, oxidative phosphorylation is uncoupled from electron flow, intramitochondrial ions and metabolites are released, and a large amplitude swelling can occur, disrupting the outer membrane and releasing intermembrane compounds.Although pore opening primarily requires the accumulation of Ca 2ϩ in the mitochondrial matrix, it is also modulated by numerous factors. For instance, P i , low ⌬⌿, thiol-oxidizing reagents, low ATP level, fatty acids, anoxia, and reaeration stress all favor pore opening, whereas thiol-reducing agents, low pH, high ⌬⌿, and divalent cations other than Ca 2ϩ counteract it (5). Inhibition of MPT is readily achieved with submicromolar concentrations of cyclosporin A (CsA) (6, 7). This highly specific effect has decisively contributed to the acceptance of the pore theory (6, 7) and is used today as the primary diagnostic trait of the classical MPT (5). The implication of mitochondria and PTP in mammalian cell death gave a new impetus to the research. For instance, cytochrome c has been shown to be released from the mitochondrial intermembrane space into the cytosol (8, 9), where it can trigger apoptosis (10). How ...

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Effect of 6‐ketocholestanol on FCCP‐ and DNP‐induced uncoupling in plant mitochondria

Cited by 24 publications

References 8 publications

On the mechanism by which 6‐ketocholestanol protects mitochondria against uncoupling‐induced Ca²⁺ efflux

On the mechanism by which 6‐ketocholestanol protects mitochondria against uncoupling‐induced Ca²⁺ efflux

BMAP-28, an Antibiotic Peptide of Innate Immunity, Induces Cell Death through Opening of the Mitochondrial Permeability Transition Pore

Occurrence and Characteristics of the Mitochondrial Permeability Transition in Plants

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Effect of 6‐ketocholestanol on FCCP‐ and DNP‐induced uncoupling in plant mitochondria

Cited by 24 publications

References 8 publications

On the mechanism by which 6‐ketocholestanol protects mitochondria against uncoupling‐induced Ca2+ efflux

On the mechanism by which 6‐ketocholestanol protects mitochondria against uncoupling‐induced Ca2+ efflux

BMAP-28, an Antibiotic Peptide of Innate Immunity, Induces Cell Death through Opening of the Mitochondrial Permeability Transition Pore

Occurrence and Characteristics of the Mitochondrial Permeability Transition in Plants

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On the mechanism by which 6‐ketocholestanol protects mitochondria against uncoupling‐induced Ca²⁺ efflux

On the mechanism by which 6‐ketocholestanol protects mitochondria against uncoupling‐induced Ca²⁺ efflux