Mitochondria-Associated Membranes (MAMs) are involved in Bax mitochondrial localization and cytochrome c release

AbstractThe distribution of the pro-apoptotic protein Bax in the outer mitochondrial membrane (OMM) is a central point of regulation of apoptosis. It is now widely recognized that parts of the endoplasmic reticulum (ER) are closely associated to the OMM, and are actively involved in different signalling processes. We adressed a possible role of these domains, called Mitochondria-Associated Membranes (MAMs) in Bax localization and fonction, by expressing the human protein in a yeast mutant deleted of MDM34, a ERMES component (ER-Mitochondria Encounter Structure). By affecting MAMs stability, the deletion of MDM34 altered Bax mitochondrial localization, and decreased its capacity to release cytochrome c. Furthermore, the deletion of MDM34 decreased the size of an uncompletely released, MAMs-associated pool of cytochrome c.

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Which Domain of VDAC2 is Necessary for Bak Insertion to the Outer Mitochondrial Membrane and tBid - Induced Cytochrome C Release?

Biophysical Journal ◽

10.1016/j.bpj.2012.11.3621 ◽

2013 ◽

Vol 104 (2) ◽

pp. 656a ◽

Cited By ~ 1

Author(s):

Shamim Naghdi ◽

Peter Varnai ◽

Soumya Sinha Roy ◽

Laszlo Hunyady ◽

Gyorgy Hajnoczky

Keyword(s):

Cytochrome C ◽

Mitochondrial Membrane ◽

Outer Mitochondrial Membrane ◽

Cytochrome C Release

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Changes in the redox state of cytochrome b5 in the outer mitochondrial membrane as a result of interaction with lipid intermediates: Role of cytochrome c

Doklady Biochemistry and Biophysics ◽

10.1134/s1607672913050086 ◽

2013 ◽

Vol 453 (1) ◽

pp. 292-296 ◽

Cited By ~ 3

Author(s):

A. D. Doroshchuk ◽

L. F. Dmitriev

Keyword(s):

Cytochrome C ◽

Mitochondrial Membrane ◽

Redox State ◽

Cytochrome B5 ◽

Outer Mitochondrial Membrane

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The Mitochondrial TOM Complex Is Required for tBid/Bax-induced Cytochrome c Release

Journal of Biological Chemistry ◽

10.1074/jbc.m703155200 ◽

2007 ◽

Vol 282 (38) ◽

pp. 27633-27639 ◽

Cited By ~ 52

Author(s):

Martin Ott ◽

Erik Norberg ◽

Katharina M. Walter ◽

Patrick Schreiner ◽

Christian Kemper ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Cytochrome C ◽

Outer Membrane ◽

Recombinant Proteins ◽

Mitochondrial Membrane ◽

Mitochondrial Outer Membrane ◽

Intermembrane Space ◽

Outer Mitochondrial Membrane ◽

Cytochrome C Release ◽

Unknown Mechanism

Cytochrome c release from mitochondria is a key event in apoptosis signaling that is regulated by Bcl-2 family proteins. Cleavage of the BH3-only protein Bid by multiple proteases leads to the formation of truncated Bid (tBid), which, in turn, promotes the oligomerization/insertion of Bax into the mitochondrial outer membrane and the resultant release of proteins residing in the intermembrane space. Bax, a monomeric protein in the cytosol, is targeted by a yet unknown mechanism to the mitochondria. Several hypotheses have been put forward to explain this targeting specificity. Using mitochondria isolated from different mutants of the yeast Saccharomyces cerevisiae and recombinant proteins, we have now investigated components of the mitochondrial outer membrane that might be required for tBid/Bax-induced cytochrome c release. Here, we show that the protein translocase of the outer mitochondrial membrane is required for Bax insertion and cytochrome c release.

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c-Myc induces cytochrome c release in Rat1 fibroblasts by increasing outer mitochondrial membrane permeability in a Bid-dependent manner

Cell Death and Differentiation ◽

10.1038/sj.cdd.4401211 ◽

2003 ◽

Vol 10 (5) ◽

pp. 599-608 ◽

Cited By ~ 19

Author(s):

I Iaccarino ◽

D Hancock ◽

G Evan ◽

J Downward

Keyword(s):

Cytochrome C ◽

Membrane Permeability ◽

Mitochondrial Membrane ◽

Dependent Manner ◽

Outer Mitochondrial Membrane ◽

Cytochrome C Release ◽

Mitochondrial Membrane Permeability

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The function of complexes between the outer mitochondrial membrane pore (VDAC) and the adenine nucleotide translocase in regulation of energy metabolism and apoptosis.

Acta Biochimica Polonica ◽

10.18388/abp.2003_3693 ◽

2003 ◽

Vol 50 (2) ◽

pp. 389-404 ◽

Cited By ~ 117

Author(s):

Mikhail Y Vyssokikh ◽

Dieter Brdiczka

Keyword(s):

Creatine Kinase ◽

Cytochrome C ◽

Mitochondrial Membrane ◽

Adenine Nucleotide ◽

Permeability Transition ◽

Adenine Nucleotide Translocase ◽

Outer Mitochondrial Membrane ◽

Cytochrome C Release ◽

Membrane Pore ◽

Contact Sites

The outer mitochondrial membrane pore (VDAC) changes its structure either voltage-dependently in artificial membranes or physiologically by interaction with the adenine nucleotide translocase (ANT) in the c-conformation. This interaction creates contact sites and leads in addition to a specific organisation of cytochrome c in the VDAC-ANT complexes. The VDAC structure that is specific for contact sites generates a signal at the surface for several proteins in the cytosol to bind with high capacity, such as hexokinase, glycerol kinase and Bax. If the VDAC binding site is not occupied by hexokinase, the VDAC-ANT complex has two critical qualities: firstly, Bax gets access to cytochrome c and secondly the ANT is set in its c-conformation that easily changes conformation into an unspecific channel (uniporter) causing permeability transition. Activity of bound hexokinase protects against both, it hinders Bax binding and employs the ANT as anti-porter. The octamer of mitochondrial creatine kinase binds to VDAC from the inner surface of the outer membrane. This firstly restrains interaction between VDAC and ANT and secondly changes the VDAC structure into low affinity for hexokinase and Bax. Cytochrome c in the creatine kinase complex will be differently organised, not accessible to Bax and the ANT is run as anti-porter by the active creatine kinase octamer. However, when, for example, free radicals cause dissociation of the octamer, VDAC interacts with the ANT with the same results as described above: Bax-dependent cytochrome c release and risk of permeability transition pore opening.

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Possible Role of Peroxynitrite in the Responses Induced by Fusicoccin in Plant Cultured Cells

Plants ◽

10.3390/plants10010182 ◽

2021 ◽

Vol 10 (1) ◽

pp. 182 ◽

Cited By ~ 1

Author(s):

Massimo Malerba ◽

Raffaella Cerana

Keyword(s):

Cytochrome C ◽

Dna Fragmentation ◽

Stress Responses ◽

Molecular Chaperones ◽

Caspase 3 ◽

Cultured Cells ◽

Acer Pseudoplatanus ◽

Cytochrome C Release ◽

Induced Stress

Fusicoccin (FC) is a well-known phytotoxin able to induce in Acer pseudoplatanus L. (sycamore) cultured cells, a set of responses similar to those induced by stress conditions. In this work, the possible involvement of peroxynitrite (ONOO−) in FC-induced stress responses was studied measuring both in the presence and in the absence of 2,6,8-trihydroxypurine (urate), a specific ONOO− scavenger: (1) cell death; (2) specific DNA fragmentation; (3) lipid peroxidation; (4) production of RNS and ROS; (5) activity of caspase-3-like proteases; and (6) release of cytochrome c from mitochondria, variations in the levels of molecular chaperones Hsp90 in the mitochondria and Hsp70 BiP in the endoplasmic reticulum (ER), and of regulatory 14-3-3 proteins in the cytosol. The obtained results indicate a role for ONOO− in the FC-induced responses. In particular, ONOO− seems involved in a PCD form showing apoptotic features such as specific DNA fragmentation, caspase-3-like protease activity, and cytochrome c release from mitochondria.

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