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ADP/ATP carrier is required for mitochondrial outer membrane permeabilization and cytochrome c release in yeast apoptosis
Author(s) -
Pereira Clara,
Camougrand Nadine,
Ma Stéphen,
Sousa Maria João,
CôrteReal Manuela
Publication year - 2007
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2007.05926.x
Subject(s) - adenine nucleotide translocator , atp–adp translocase , biology , cytochrome c , mitochondrial apoptosis induced channel , voltage dependent anion channel , inner mitochondrial membrane , mitochondrion , mitochondrial carrier , microbiology and biotechnology , biochemistry , translocase of the inner membrane , yeast , translocase , mitochondrial permeability transition pore , inner membrane , bacterial outer membrane , mitochondrial membrane transport protein , apoptosis , programmed cell death , gene , chromosomal translocation , escherichia coli
Summary Adenine nucleotide translocator (ANT) is a mitochondrial inner membrane protein involved in the ADP/ATP exchange and is a component of the mitochondrial permeability transition pore (PTP). In mammalian apoptosis, the PTP can mediate mitochondrial outer membrane permeabilization (MOMP), which is suspected to be responsible for the release of apoptogenic factors, including cytochrome c. Although release of cytochrome c in yeast apoptosis has previously been reported, it is not known how it occurs. Herein we used yeast genetics to investigate whether depletion of proteins putatively involved in MOMP and cytochrome c release affects these processes in yeast. While deletion of POR1 (yeast voltage‐dependent anion channel) enhances apoptosis triggered by acetic acid, H 2 O 2 and diamide, CPR3 (mitochondrial cyclophilin) deletion had no effect. Absence of ADP/ATP carrier (AAC) proteins, yeast orthologues of ANT, protects cells exposed to acetic acid and diamide but not to H 2 O 2 . Expression of a mutated form of Aac2p (op1) exhibiting very low ADP/ATP translocase activity indicates that AAC's pro‐death role does not require translocase activity. Absence of AAC proteins impairs MOMP and release of cytochrome c , which, together with other mitochondrial inner membrane proteins, is degraded. Our findings point to a crucial role of AAC in yeast apoptosis.