Mitochondrial AAA-Type Protease Yme1p Is Involved in Bax Effects on Cytochrome c Oxidase

Manon, Stéphen; Priault, Muriel; Camougrand, Nadine

doi:10.1006/bbrc.2001.6120

Cited by 28 publications

(18 citation statements)

References 28 publications

(30 reference statements)

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“…In fact, COX II participates in CytC binding (Bisson et al, 1977) and the absence of CytC seems to destabilize COX II, making it susceptible to degradation (Pearce and Sherman, 1995). Manon et al (2001) reported very recently that Bax-induced CytC release is directly involved in the decrease of COX activity by activating the mitochondrial AAA-type protease Yme1p, which leads to COX II degradation.…”

Section: Discussionmentioning

confidence: 99%

CytochromecRelease and Mitochondria Involvement in Programmed Cell Death Induced by Acetic Acid inSaccharomyces cerevisiae

Ludovico

Rodrigues

Almeida

et al. 2002

MBoC

357

365

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Evidence is presented that mitochondria are implicated in the previously described programmed cell death (PCD) process induced by acetic acid in Saccharomyces cerevisiae. In yeast cells undergoing a PCD process induced by acetic acid, translocation of cytochrome c (CytC) to the cytosol and reactive oxygen species production, two events known to be proapoptotic in mammals, were observed. Associated with these events, reduction in oxygen consumption and in mitochondrial membrane potential was found. Enzymatic assays showed that the activity of complex bc 1 was normal, whereas that of cytochrome c oxidase (COX) was strongly decreased. This decrease is in accordance with the observed reduction in the amounts of COX II subunit and of cytochromes aϩa 3 . The acetic acid-induced PCD process was found to be independent of oxidative phosphorylation because it was not inhibited by oligomycin treatment. The inability of S. cerevisiae mutant strains (lacking mitochondrial DNA, heme lyase, or ATPase) to undergo acetic acid-induced PCD and in the ATPase mutant (knockout in ATP10) the absence of CytC release provides further evidence that the process is mediated by a mitochondria-dependent apoptotic pathway. The understanding of the involvement of a mitochondria-dependent apoptotic pathway in S. cerevisiae PCD process will be most useful in the further elucidation of an ancestral pathway common to PCD in metazoans.

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Section: Discussionmentioning

confidence: 99%

CytochromecRelease and Mitochondria Involvement in Programmed Cell Death Induced by Acetic Acid inSaccharomyces cerevisiae

Ludovico

Rodrigues

Almeida

et al. 2002

MBoC

357

365

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“…Mitochondrial respiration and yeast components of the permeability transition pore in Bax-induced cell death Similar to treatment with acetic acid, Bax expression comes along with changes in mitochondrial membrane potential [24] and reduction of COX activity [25], probably due to a reduced amount of Cox2p [63]. It was demonstrated that the mitochondrial protease Yme1p is responsible for the cleavage of Cox2p and that deletion of YME1 delays Bax-induced cell death [63]. The requirement of oxidative phosphorylation and cytochrome c in Bax mediated cell death in yeast has frequently been addressed.…”

Section: Mitochondrial Cell Death Regulation By Heterologous Expressimentioning

confidence: 99%

The mitochondrial pathway in yeast apoptosis

et al. 2007

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Mitochondria are not only important for the energetic status of the cell, but are also the fatal organelles deciding about cellular life and death. Complex mitochondrial features decisive for cell death execution in mammals are present and functional in yeast: AIF and cytochrome c release to the cytosol, mitochondrial fragmentation as well as mitochondrial hyperpolarisation followed by an oxidative burst, and breakdown of mitochondrial membrane potential. The easy accessibility of mitochondrial manipulations such as repression of respiration by growing yeast on glucose or deletion of mitochondrial DNA (rho 0 ) on the one hand and the unique ability of yeast cells to grow on nonfermentable carbon sources by switching on mitochondrial respiration on the other hand have made yeast an excellent tool to delineate the necessity for mitochondria in cell death execution. Yeast research indicates that the connection between mitochondria and apoptosis is intricate, as abrogation of mitochondrial function can be either deleterious or beneficial for the cell depending on the specific context of the death scenario. Surprisingly, mitochondrion dependent yeast apoptosis currently helps to understand the aetiology (or the complex biology) of lethal cytoskeletal alterations, ageing and neurodegeneration. For example, mutation of mitochondrial superoxide dismutase or CDC48/VCP mutations, both T. Eisenberg · S. Büttner · F. Madeo ( ) Institute of Molecular Biosciences, Universitaetsplatz 2, University of Graz, 8010 Graz, Austria e-mail: frank.madeo@uni-graz.at G. Kroemer Apoptosis, Cancer, and Immunity Unit, Institut Gustave Roussy, Faculté Paris Sud-Université, Institut National de la Santé et de la Recherche Médicale, Paris XI, France implicated in several neurodegenerative disorders, are associated with mitochondrial impairment and apoptosis in yeast.

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“…4A for typical recordings) The concentration of cytochromes was calculated from the spectra at 550 -540 nm (⌬⑀ ϭ 18,000 M Ϫ1 ⅐cm Ϫ1 ) for cytochrome c, 561-575 nm (⌬⑀ ϭ 18,000 M Ϫ1 ⅐cm Ϫ1 ) for cytochrome b, and 603-630 nm (⌬⑀ ϭ 24,000 M Ϫ1 ⅐cm Ϫ1 ) for cytochrome aa 3 , respectively. The advantage of this method is that cytochrome b, which is a membrane protein, is not released nor degraded (34) and serves as an internal control to the experiment.…”

Section: G10v/g11w/ G12vmentioning

confidence: 99%

Studies of the Interaction of Substituted Mutants of BAX with Yeast Mitochondria Reveal That the C-terminal Hydrophobic α-Helix Is a Second ART Sequence and Plays a Role in the Interaction with Anti-apoptotic BCL-xL

Arokium

Camougrand

Vallette

et al. 2004

Journal of Biological Chemistry

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The role of the two ends of the pro-apoptotic protein BAX in its interaction with mitochondria was challenged by assaying substituted mutants in yeast cells for the ability to bind and insert into the mitochondrial membrane and to promote the release of cytochrome c. Mutations at the N-terminal end confirmed the inhibitory function of this zone, known as apoptotic regulation of targeting (ART). On the other hand, mutations at the C-terminal end of the protein support the hypothesis that the hydrophobic helix ␣9 is not required for the insertion of BAX. In addition, three mutations (a T174D single substitution in the helix ␣9, a K189E/K190E double substitution at the end of the protein, and a P168A mutation in the loop before ␣9) exhibited a strong binding capacity, a strong insertion, as well as high ability to induce cytochrome c release. Considering the positions of these mutations and their potential effect on the movement of helix ␣9, we propose that the C-terminal end of the protein behaves like a second ART. Also, opposite to a mutation that changes the conformation of the N-terminal ART, the mutations in the C-terminal part of the protein impaired the inhibitory effect of antiapoptotic BCL-x L over BAX insertion, suggesting that the conformation of the ␣9-helix plays a significant role in BAX/BCL-x L interaction.Apoptosis, the main form of programmed cell death, is a highly regulated phenomenon. It is now largely accepted that mitochondria play a key role in regulating the apoptotic process by controlling the release of several proteins, termed apoptogenic factors, required for the acquisition of apoptotic hallmarks (for review see Refs. 1 and 2). This release strictly depends on the action of a family of proteins, termed the BCL-2 family, that modulates the permeability of the outer mitochondrial membrane to the apoptogenic factors (for review see Refs. 3 and 4). Moreover, the alteration of the bioenergetic capacity of mitochondria following the action of BCL-2 family members is thought to be further involved in the regulation of apoptosis by the production of reactive oxygen species (for review see Ref. 5) or the release of Ca 2ϩ (for review see Ref. 6).Among the BCL-2 family members, the pro-apoptotic protein BAX plays a crucial role (for review see Ref. 7). BAX is expressed at basal levels in nearly all mammalian cells. In healthy cells, it behaves as a soluble protein and is localized in the cytosol; following apoptotic induction, the protein is translocated to the mitochondrial outer membrane where it behaves as a membrane-inserted protein (8, 9) and actively participates in the release of apoptogenic factors. The molecular mechanisms governing the cytosol-to-mitochondria translocation of BAX therefore appear as a critical regulation in the implementation of apoptosis.The changes in the physical properties of BAX accompanying its translocation strongly support the hypothesis that profound conformational changes are the basis of the change in the localization of the protein. Analysis of the primary...

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Mitochondrial AAA-Type Protease Yme1p Is Involved in Bax Effects on Cytochrome c Oxidase

Cited by 28 publications

References 28 publications

CytochromecRelease and Mitochondria Involvement in Programmed Cell Death Induced by Acetic Acid inSaccharomyces cerevisiae

CytochromecRelease and Mitochondria Involvement in Programmed Cell Death Induced by Acetic Acid inSaccharomyces cerevisiae

The mitochondrial pathway in yeast apoptosis

Studies of the Interaction of Substituted Mutants of BAX with Yeast Mitochondria Reveal That the C-terminal Hydrophobic α-Helix Is a Second ART Sequence and Plays a Role in the Interaction with Anti-apoptotic BCL-xL

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